Transcriptionally linked simultaneous overexpression of P450 genes for broad-spectrum herbicide resistance.

Broad-spectrum herbicide resistance (BSHR), often linked to weeds with metabolism-based herbicide resistance, poses a threat to food production. Past studies have revealed that overexpression of catalytically promiscuous enzymes explains BSHR in some weeds; however, the mechanism of BSHR expression remains poorly understood. Here, we investigated the molecular basis of high-level resistance to diclofop-methyl in BSHR late watergrass (Echinochloa phyllopogon) found in the United States, which cannot be solely explained by the overexpression of promiscuous cytochrome P450 monooxygenases CYP81A12/21. The BSHR late watergrass line rapidly produced 2 distinct hydroxylated diclofop acids, only 1 of which was the major metabolite produced by CYP81A12/21. RNA-seq and subsequent reverse transcription quantitative PCR (RT-qPCR)-based segregation screening identified the transcriptionally linked overexpression of a gene, CYP709C69, with CYP81A12/21 in the BSHR line. The gene conferred diclofop-methyl resistance in plants and produced another hydroxylated diclofop acid in yeast (Saccharomyces cerevisiae). Unlike CYP81A12/21, CYP709C69 showed no other herbicide-metabolizing function except for a presumed clomazone-activating function. The overexpression of the 3 herbicide-metabolizing genes was also identified in another BSHR late watergrass in Japan, suggesting a convergence of BSHR evolution at the molecular level. Synteny analysis of the P450 genes implied that they are located at mutually independent loci, which supports the idea that a single trans-element regulates the 3 genes. We propose that transcriptionally linked simultaneous overexpression of herbicide-metabolizing genes enhances and broadens the metabolic resistance in weeds. The convergence of the complex mechanism in BSHR late watergrass from 2 countries suggests that BSHR evolved through co-opting a conserved gene regulatory system in late watergrass.

Characterization of 2 linear peptides without disulfide bridges from the venom of the spider Lycosa poonaensis (Lycosidae).

Spider venom is a complex mixture of bioactive components, in which peptides play an important role by showing neurotoxicity or cytotoxicity. Disulfide-rich peptides are major components in the venom, but linear peptides without disulfide bridges are also present and often show antimicrobial activity. In this study, we analyzed the venom of the spider Lycosa poonaensis (Lycosidae) to find novel antimicrobial peptides using mass spectrometry. The result revealed that 120 out of 401 detected components were nondisulfide-bridged peptides. From them, the sequence of 2 peptides (lyp2370 and lyp1987) were determined by MS/MS analysis. The biological activity test revealed that lyp2370 has only weak antibacterial activity. On the other hand, lyp1987, which is identical to M-lycotoxin-Ls3b from the Lycosa singoriensi venom, showed significant antibacterial activity. The weak activity of lyp2370 was found to be due to the presence of a Glu residue on the hydrophilic face of its amphipathic α-helical structure.

A Fluorescent Compound from the Exuviae of the Scorpion, Liocheles australasiae.

Most scorpions fluoresce under UV light. To date, two types of fluorescent compounds have been identified in scorpions, but it has been assumed that other unknown compounds may be responsible for the fluorescence. In this study, we isolated a fluorescent compound from the exuviae of the scorpion Liocheles australasiae identified as a macrocyclic diphthalate ester with a molecular mass of 496.2 Da. The same compound was also detected in extracts from four other scorpion species. This suggests that this compound is shared by multiple scorpion species, although its contribution to the cuticle fluorescence may be relatively small.

Neuromyelitis optica spectrum disorder safely and successfully treated with satralizumab during pregnancy and breastfeeding: a case report.

Background: Satralizumab, a monoclonal antibody that recognizes interleukin-6 receptors, is known to reduce the relapse rate in neuromyelitis optica spectrum disorder (NMOSD), but its safety during pregnancy has not been established. We present the case of an NMOSD patient who safely completed pregnancy, parturition, and breastfeeding under satralizumab treatment. Importantly, satralizumab transfer to umbilical cord blood, infant serum, or breast milk was not observed. Case presentation: A 37-year-old Japanese female developed anti-aquaporin 4 antibody-positive NMOSD with left optic neuritis. Despite responding to steroid and azathioprine therapy, she experienced moon face and weight gain and desired the prompt reduction of the steroid dosage. She also wanted to conceive a child with a safe and preferably early pregnancy and parturition. Because pregnancy and parturition after the onset of NMOSD elevate the risk of relapse and miscarriage, treatment with satralizumab was initiated with the patient's consent. She experienced normal parturition and continued with satralizumab, steroid, and azathioprine treatments while breastfeeding without experiencing any relapses. Concentrations of satralizumab in the umbilical cord blood, infant serum, and breast milk were below the detection sensitivity. Conclusion: These findings suggest that satralizumab may be safe and effective for the perinatal management of NMOSD, especially when there are concerns about continuing pregnancy and the risk of relapse after parturition.

Hyperacute ischemic stroke treated with carotid-carotid artery bypass surgery "case report".

Thrombolytic therapy using heparin, urokinase, and tissue plasminogen activator (tPA) has been the standard treatment for hyperacute ischemic stroke (HIS) with worsening carotid artery stenosis. In recent years, endovascular treatments (thrombectomy and carotid artery stenting) have attracted attention, and neurosurgeons are increasingly participating in these treatments. A 70-year-old Japanese male presented to our hospital with aphasia and right hemiparesis. Emergency computed tomography ([CT] CT angiography and perfusion CT) revealed a small infarct core and a large hemiparesis due to occlusion near the left common carotid artery orifice. Because of hemorrhagic sequelae, tPA was not administered, and emergency endovascular treatment failed. Therefore, a bilateral common carotid artery bypass surgery was performed. Revascularization was performed within 51 min of the start of the surgery, and the time from onset to revascularization was 5 h. Aphasia and right hemiparesis resolved immediately after surgery. The only sequela observed was mild dyskinesia. Our report is the first to show that bilateral common carotid artery bypass is a novel and effective treatment for HIS.

Treatment outcomes of IgG4-producing marginal zone B-cell lymphoma: a retrospective case series.

IgG4-producing marginal zone B-cell lymphomas (MZLs) have been recently proposed as a subtype of MZLs. Despite the abundant literature on pathophysiological features of this type of lymphoma, only a few retrospective studies pertaining to the treatment outcomes have been reported, and its prognosis remains unclear. We retrospectively analyzed seven patients with IgG4-producing MZLs diagnosed at our institute, with specific reference to treatment and outcomes. The median age was 69.0 years (55-79), and all were males. The median follow-up period was 66.6 months (8-121). All patients had localized disease; four patients had tumors of the ocular adnexa, whereas two had retroperitoneal tumors. Five patients were treated with irradiation (30 Gy/15 fr) (n = 4) or surgery (n = 1), resulting in tumor reduction. Two patients were treated by chemotherapy or irradiation. Among them, one commenced rituximab monotherapy, which led to an inadequate reduction of the tumor. Subsequent irradiation induced complete response (CR). The other patient experienced repeated relapses during follow-up and finally achieved CR by combination chemotherapy. Treatment was well tolerated in all cases, and none of the patients showed disease progression at the last follow-up visit. Our results indicate that the standard treatments for MZLs are generally appropriate for IgG4-producing MZL.

Isolation and Characterization of Insecticidal Toxins from the Venom of the North African Scorpion, Buthacus leptochelys.

Various bioactive peptides have been identified in scorpion venom, but there are many scorpion species whose venom has not been investigated. In this study, we characterized venom components of the North African scorpion, Buthacus leptochelys, by mass spectrometric analysis and evaluated their insect toxicity. This is the first report of chemical and biological characterization of the B. leptochelys venom. LC/MS analysis detected at least 148 components in the venom. We isolated four peptides that show insect toxicity (Bl-1, Bl-2, Bl-3, and Bl-4) through bioassay-guided HPLC fractionation. These toxins were found to be similar to scorpion α- and ß-toxins based on their N-terminal sequences. Among them, the complete primary structure of Bl-1 was determined by combination of Edman degradation and MS/MS analysis. Bl-1 is composed of 67 amino acid residues and crosslinked with four disulfide bonds. Since Bl-1 shares high sequence similarity with α-like toxins, it is likely that it acts on Na+ channels of both insects and mammals.

Visualization of aneurysmal contours and perianeurysmal environment with conventional and transparent 3D MR cisternography.

We have developed conventional and transparent 3D MR cisternography to investigate the spatial relationship between the contours of aneurysmal complex and the perianeurysmal structures including the cranial nerves, dural fold, cranial base bone, and brain parenchyma. Volume data obtained by a T2-weighted 3D fast spin-echo sequence were reconstructed by using a perspective volume-rendering algorithm with a transluminal imaging technique. 3D MR cisternograms provide useful anatomic information in the therapeutic and follow-up management of unruptured cerebral aneurysms.

Influence of perianeurysmal environment on the deformation and bleb formation of the unruptured cerebral aneurysm: assessment with fusion imaging of 3D MR cisternography and 3D MR angiography.

BACKGROUND AND PURPOSE: Surface irregularity and bleb formation are anatomical factors that are associated with aneurysm rupture. The perianeurysmal environment has been proposed as one factor that may influence aneurysm morphology. We have developed a fusion imaging technique of 3D MR cisternography and angiography that allows clear visualization of an aneurysm and its environment. This technique may prove useful in further understanding of the natural history of intracranial aneurysms. METHODS: Fusion images of 3D MR cisternography and angiography were reconstructed by a perspective volume-rendering algorithm from the volume datasets of MR cisternography, obtained by a T2-weighted 3D fast spin-echo sequence, and coordinated MR angiography, by a 3D time-of-flight sequence. On the fusion images, the anatomic relationship of an aneurysm to the perianeurysmal structures was assessed, and the influence of perianeurysmal environment on the deformation and bleb formation of the aneurysm was investigated. RESULTS: Marked and minor deformation and bleb formation of the aneurysmal dome were found at the areas confronted or adjacent to a certain contact with perianeurysmal structures, including cranial nerves, brain parenchyma, cranial base bones, petroclinoidal dural folds, and dura mater. CONCLUSION: Fusion images of 3D MR cisternography and angiography can depict the contact of an aneurysm with its perianeurysmal environment; this may provide an additional parameter in consideration for the natural history of cerebral aneurysms.

[Assessment of the perianeurysmal environment of unruptured internal carotid-posterior communicating artery aneurysms with fusion imaging of three-dimensional magnetic resonance cisternography and angiography].

The anatomical relationship of an unruptured internal carotid-posterior communicating artery aneurysm and the perianeurysmal environment was investigated by using three-dimensional (3D) magnetic resonance cisternography (MRC), angiography (MRA) and newly developed fusion images of 3D MRC and 3D MRA. Contact of an aneurysm with the adjacent intra- and pericisternal structures was observed in cases with the aneurysm developing and extending beyond the capacity of the surrounding subarachnoid space. Deformation and bleb formation of the aneurysmal dome was depicted at the dome in contact with the perianeurysmal environment, including the tentorial edge, the anterior petroclinoid dural fold, the oculomotor nerve, the posterior clinoid process, the dorsum sellae and the cranial base bone. By using the fusion imaging technique of 3D MRC and 3D MRA, assessment of the contact of an unruptured cerebral aneurysm with its perianeurysmal environment can be made. Such contact gives ride to risk of deformation and bleb formation of the aneurysmal dome; and may result in cranial nerve symptoms and accelerate rupture from an unruptured cerebral aneurysm.

[Assessment of the signal intensity distribution pattern within the unruptured cerebral aneurysms using color-coded 3D MR angiography].

To evaluate the interaction between the MR signal intensity distribution pattern and bleb formation/ deformation of the aneurysmal dome, fifty cases of the unruptured cerebral aneurysms were investigated with the color-coded 3D MR angiography. Patterns were categorized into central-type, neck-type and peripheral-type according to the distribution of MR signals with low-, moderate- and high signal intensity areas. Imaging analysis revealed the significant relationship (P < 0.02) of the peripheral-type aneurysms to the bleb formation and deformation of the dome, compared with those of central- and neck-type. Additionally, peripheral-type signal intensity distribution pattern was shown with aneurysms harboring relatively large dome size and lateral-type growth including internal carotid aneurysms. Prospective analysis of intraaneurysmal flow pattern with the color-coded 3D MR angiography may provide patient-specific analysis of intraaneurysmal flow status in relation to the morphological change of the corresponding aneurysmal dome in the management of unruptured cerebral aneurysms.