Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism

TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV (MLIV). In the present study, we determined the cryo-electron microscopy (cryo-EM) structures of Mus musculus TRPML1 (mTRPML1) in lipid nanodiscs and Amphipols. Two distinct states of mTRPML1 in Amphipols are added to the closed state, on which could represent two different confirmations upon activation and regulation. The polycystin-mucolipin domain (PMD) may sense the luminal/extracellular stimuli and undergo a "move upward" motion during endocytosis, thus triggering the overall conformational change in TRPML1. Based on the structural comparisons, we propose TRPML1 is regulated by pH, Ca, and phosphoinositides in a combined manner so as to accommodate the dynamic endocytosis process.

Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen α

Bone sialoprotein-binding protein (Bbp), a MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family protein expressed on the surface of Staphylococcus aureus (S. aureus), mediates adherence to fibrinogen α (Fg α), a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp(273-598) and Bbp(273-598)-Fg α(561-575) complex at a resolution of 2.03 Å and 1.45 Å, respectively. Apo-Bbp(273-598) contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional D1 strand in N2 domain and D1' and D2' strands in N3 domain. The peptide mapped to the Fg α(561-575) bond to Bbp(273-598) on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a β-strand G'' covering the ligand upon ligand binding. Bbp(Ala298-Gly301) in the N2 domain of the Bbp(273-598)-Fg α(561-575) complex, which is a loop in the apo-form, formed a short α-helix to interact tightly with the peptide. In addition, Bbp(Ser547-Gln561) in the N3 domain moved toward the binding groove to make contact directly with the peptide, while Bbp(Asp338-Gly355) and Bbp(Thr365-Tyr387) in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process.

Efficacy of acupuncture intervention on urinary retention after spinal anesthesia / 中国针灸

<p><b>OBJECTIVE</b>To observe the acupuncture effect on urinary retention after spinal anesthesia.</p><p><b>METHODS</b>One hundred and fifty-four patients with spinal anesthesia were randomized into an observation group (80 cases) and a control group (74 cases). In the observation group, the electroacupuncture was applied to bilateral Fushe (SP 13) and Shuidao (ST 28); 2 Hz/50 Hz, retaining for 30 min. One treatment was required. In the control group, no any intervention was applied after operation. The incidence of the postoperative urinary retention, the time of the first automatic micturition since 30 min after spinal anesthesia, the volume of the first micturition, the postoperative urine condition, the lower abdominal distention, incomplete urination and the others were observed.</p><p><b>RESULTS</b>The incidence of urinary retention in the observation group was lower than that in the control group; the first automatic micturition in 30 min after spinal anesthesia was earlier than that in the control group; the comfortable urination rate was higher than that in the control group; the incidence of incomplete urination and lower abdominal distention were lower than those in the control group. The differences were significant in comparison of the two groups (all P<0.05).</p><p><b>CONCLUSION</b>Acupuncture apparently shortens the time of first automatic micturition after spinal anesthesia and promotes the recovery of bladder urinary reflection. This therapy acts on promoting urination and reducing postoperative urinary retention.</p>

Detection of vaginal discharge by ultra-high power microscope and conventional microscope / 中国医疗器械杂志

<p><b>OBJECT</b>To study the significance of the ultra-high power microscope in the examination of vaginal discharge.</p><p><b>METHODS</b>By the ACT-2000 ultra-high power microscope system and Olympus CX21 microscope, the vaginal discharge of 1,100 gynaecology out-patients was examined respectively.</p><p><b>RESULTS</b>The positive rate of mould in the patients was 11.55% by CX21 and was 20.27% by ACT-2000, respectively. The positive rate of trichomonas vaginalis was 2.55% by CX21 and 3.0% by ACT-2000, respectively. The clue cell was detected in 11.27% of the patients by ACT-2000, but no such cell reported by CX21. Totally, positive results were obtained in 14.09% of the patients by CX21 and 32.55% by ACT-2000.</p><p><b>CONCLUSION</b>By using the ultra-high power microscope, the positive result can be increased obviously in the examination of vaginal discharge. It is very important in clinical practices.</p>