Effective legume-rhizobia symbiosis depends on efficient nutrient exchange. Rhizobia need to synthesize iron-containing proteins for symbiotic nitrogen fixation (SNF) in nodules, which depends on host plant-mediated iron uptake into the symbiosome.We functionally investigated a pair of vacuolar iron transporter like (VTL) genes, GmVTL1a/b, in soybean (Glycine max) and evaluated their contributions to SNF, including investigations of gene expression patterns, subcellular localization, and mutant phenotypes. Though both GmVTL1a/b genes were specifically expressed in the fixation zone of the nodule, GmVTL1a was the lone member to be localized at the tonoplast of tobacco protoplasts, and shown to facilitate ferrous iron transport in yeast. GmVTL1a targets the symbiosome in infected cells, as verified by in situ immunostaining. Two vtl1 knockout mutants had lower iron concentrations in nodule cell sap and peribacteroid units than in wild-type plants, suggesting that GmVTL1 knockout inhibited iron import into symbiosomes. Furthermore, GmVTL1 knockout minimally affected soybean growth under nonsymbiotic conditions, but dramatically impaired nodule development and SNF activity under nitrogen-limited and rhizobia-inoculation conditions, which eventually led to growth retardation.Taken together, these results demonstrate that GmVTL1a is indispensable for SNF in nodules as a transporter of ferrous iron from the infected root cell cytosol to the symbiosome.

Background and Purpose: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated. Methods: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed. Results: Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year. Conclusions: A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.

The aim of the study was to assess the capacity of dynamic cerebral autoregulation (dCA) in asymptomatic patients with unilateral middle cerebral artery (MCA) stenosis.Fifty-seven patients with asymptomatic mild, moderate, and severe unilateral MCA stenosis and 8 patients with symptomatic severe unilateral MCA stenosis diagnosed by transcranial Doppler were enrolled. Twenty-four healthy volunteers served as controls. The noninvasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously from each subject in the supine position. Transfer function analysis was applied to determine the autoregulatory parameters (phase difference [PD] and gain).The PD values in the severe stenosis groups were significantly lower than those of the control group (60.71 ± 18.63°), the asymptomatic severe stenosis group was impaired ipsilaterally (28.94 ± 27.43°, P < 0.001), and the symptomatic severe stenosis group was impaired bilaterally (13.74 ± 19.21°, P < 0.001; 19.68 ± 14.50°, P = 0.006, respectively). The PD values in the mild and moderate stenosis groups were not significantly different than the controls (44.49 ± 27.93°; 48.65 ± 25.49°, respectively). The gain values in the mild and moderate groups were higher than in the controls (1.00 ± 0.58 cm/s/mm Hg vs 0.86 ± 0.34 cm/s/mm Hg, and 1.20 ± 0.59 cm/s/mm Hg vs 0.86 ± 0.34 cm/s/mm Hg, respectively). The gain values in the severe stenosis groups were significantly lower than that in the control group: the asymptomatic severe stenosis group was lower bilaterally (0.56 ± 0.32 cm/s/mm Hg, P = 0.003; 0.60 ± 0.32 cm/s/mm Hg, P < 0.05, respectively), whereas the symptomatic severe group was lower unilaterally (on the contralateral side) (0.53 ± 0.43 cm/s/mm Hg, P < 0.05).In asymptomatic patients with unilateral MCA stenosis, only the dCA of the severe stenosis was ipsilaterally impaired. Acute stroke may aggravate the impaired dCA and even spread contralaterally.