A Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont.

Consumption of glucosinolates, pro-drug-like metabolites abundant in Brassica vegetables, has been associated with decreased risk of certain cancers. Gut microbiota have the ability to metabolize glucosinolates, generating chemopreventive isothiocyanates. Here, we identify a genetic and biochemical basis for activation of glucosinolates to isothiocyanates by Bacteroides thetaiotaomicron, a prominent gut commensal species. Using a genome-wide transposon insertion screen, we identified an operon required for glucosinolate metabolism in B. thetaiotaomicron. Expression of BT2159-BT2156 in a non-metabolizing relative, Bacteroides fragilis, resulted in gain of glucosinolate metabolism. We show that isothiocyanate formation requires the action of BT2158 and either BT2156 or BT2157 in vitro. Monocolonization of mice with mutant BtΔ2157 showed reduced isothiocyanate production in the gastrointestinal tract. These data provide insight into the mechanisms by which a common gut bacterium processes an important dietary nutrient.

Biosynthesis of cabbage phytoalexins from indole glucosinolate.

Brassica crop species are prolific producers of indole-sulfur phytoalexins that are thought to have an important role in plant disease resistance. These molecules are conspicuously absent in the model plant Arabidopsis thaliana, and little is known about the enzymatic steps that assemble the key precursor brassinin. Here, we report the minimum set of biosynthetic genes required to generate cruciferous phytoalexins starting from the well-studied glucosinolate pathway. In vitro biochemical characterization revealed an additional role for the previously described carbon-sulfur lyase SUR1 in processing cysteine-isothiocyanate conjugates, as well as the S-methyltransferase DTCMT that methylates the resulting dithiocarbamate, together completing a pathway to brassinin. Additionally, the ß-glucosidase BABG that is present in Brassica rapa but absent in Arabidopsis was shown to act as a myrosinase and may be a determinant of plants that synthesize phytoalexins from indole glucosinolate. Transient expression of the entire pathway in Nicotiana benthamiana yields brassinin, demonstrating that the biosynthesis of indole-sulfur phytoalexins can be engineered into noncruciferous plants. The identification of these biosynthetic enzymes and the heterologous reconstitution of the indole-sulfur phytoalexin pathway sheds light on an important pathway in an edible plant and opens the door to using metabolic engineering to systematically quantify the impact of cruciferous phytoalexins on plant disease resistance and human health.

Multilab EcoFAB study shows highly reproducible physiology and depletion of soil metabolites by a model grass.

There is a dynamic reciprocity between plants and their environment: soil physiochemical properties influence plant morphology and metabolism, and root morphology and exudates shape the environment surrounding roots. Here, we investigate the reproducibility of plant trait changes in response to three growth environments. We utilized fabricated ecosystem (EcoFAB) devices to grow the model grass Brachypodium distachyon in three distinct media across four laboratories: phosphate-sufficient and -deficient mineral media allowed assessment of the effects of phosphate starvation, and a complex, sterile soil extract represented a more natural environment with yet uncharacterized effects on plant growth and metabolism. Tissue weight and phosphate content, total root length, and root tissue and exudate metabolic profiles were consistent across laboratories and distinct between experimental treatments. Plants grown in soil extract were morphologically and metabolically distinct, with root hairs four times longer than with other growth conditions. Further, plants depleted half of the metabolites investigated from the soil extract. To interact with their environment, plants not only adapt morphology and release complex metabolite mixtures, but also selectively deplete a range of soil-derived metabolites. The EcoFABs utilized here generated high interlaboratory reproducibility, demonstrating their value in standardized investigations of plant traits.

Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis.

Phytoalexins are abundant in edible crucifers and have important biological activities, yet no dedicated gene for their biosynthesis is known. Here, we report two new cytochromes P450 from Brassica rapa (Chinese cabbage) that catalyze unprecedented S-heterocyclizations in cyclobrassinin and spirobrassinin biosynthesis. Our results provide genetic and biochemical insights into the biosynthesis of a prominent pair of dietary metabolites and have implications for pathway discovery across >20 recently sequenced crucifers.

Imaging correlates of neural control of ocular movements.

The purpose of oculomotor movements is maintenance of clear images on the retina. Beyond this oversimplification, it requires several different types of ocular movements and reflexes to focus objects of interest to the fovea-the only portion of retina capable of sharp and clear vision. The different movements and reflexes that execute this task are the saccades, smooth pursuit movements, fixation, accommodation, and the optokinetic and vestibulo-ocular reflexes. Many different centres in the cerebrum, cerebellum, brainstem and thalami, control these movements via different pathways. At the outset, these mechanisms appear dauntingly complex to a radiologist. However, only a little effort could make it possible to understand these neural controls and empower the reading session. The following review on ocular movements and their neural control will enable radiologists and clinicians to correlate lesions with clinical deficits effectively without being swamped by exhaustive detail. Key Points • Knowledge of cortical and subcortical areas controlling ocular movements is important. • Understanding of neural control of ocular movements makes a good foundation. • Awareness of anatomic areas controlling ocular movements helps in clinico-radiologic correlation.

Intervertebral disc height loss demonstrates the threshold of major pathological changes during degeneration.

PURPOSE: Quantitative MRI techniques were utilized to study intervertebral disc degeneration. Main focus was to develop a novel approach to quantify disc height loss associated with disc degeneration. Currently there is no universally accepted metric of degeneration based on measurement of disc height. Such quantitative imaging methods would complement qualitative visual assessment methods currently used and offer a valuable diagnostic tool. METHODS: 51 adult participants took part in this MRI study. T2 weighted images were used to obtain disc height index (DHI) and also a semi-quantitative metric based on relative voxel intensities. For DHI, each disc was given a score based on standard deviations from the mean DHI of healthy discs. Diffusion Weighted MRI was used to assess morphological changes in the nucleus pulposus. Conventional Pfirrmann classification was used as the gold standard to assess these quantitative approaches. RESULTS: At deviations of up to 1.5σ below normative disc height, levels of apparent diffusion coefficient (ADC) and normalized T2 intensity were maintained. Once disc compression reached 1.5σ, there was a massive drop in ADC and normalized T2 intensity. Pfirrmann degeneration scores also increased after the 1.5σ mark. CONCLUSIONS: This study provides new, unbiased quantitative imaging tools to assess disc degeneration. We observed that these quantitative MRI measures indicate a threshold beyond which major pathological changes take place concurrently. Combined information from DHI, ADC and T2 images construct a set of novel biomarkers that could be used to identify degenerating discs that are approaching the threshold and possibly intervene before major pathologic changes occur.

Changes in perfusion and diffusion in the endplate regions of degenerating intervertebral discs: a DCE-MRI study.

PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) was used to investigate the associations between intervertebral disc degeneration and changes in perfusion and diffusion in the disc endplates. METHODS: 56 participants underwent MRI scans. Changes in DCE-MRI signal enhancement in the endplate regions were analyzed. Also, a group template was generated for the endplates and enhancement maps were registered to this template for group analysis. RESULTS: DCE-MRI enhancement changed significantly in cranial endplates with increased degeneration. A similar trend was observed for caudal endplates, but it was not significant. Group-averaged enhancement maps revealed major changes in spatial distribution of endplate perfusion and diffusion with increasing disc degeneration especially in peripheral endplate regions. CONCLUSIONS: Increased enhancement in the endplate regions of degenerating discs might be an indication of ongoing damage in these tissues. Therefore, DCE-MRI could aid in understanding the pathophysiology of disc degeneration. Moreover, it could be used in the planning of novel treatments such as stem cell therapy.

Minimum set of cytochromes P450 for reconstituting the biosynthesis of camalexin, a major Arabidopsis antibiotic.

Bringing it all together: The missing key step in the biosynthesis of camalexin was uncovered by in vitro biochemical characterization. The coupling of Trp- and Cys-derived fragments through CS bond formation is promoted by an unusual cytochrome P450 CYP71A13. The in vitro reconstitution of the camalexin biosynthesis (left) from Trp and Cys was achieved using just three cytochromes P450. IAN=indole-3-acetonitrile.

Why Is This Auntminnie a Diagnostic Conundrum?: A Knowledge-Based Approach to Balo's Concentric Sclerosis From Reports of 3 Cases and Pooled Data From 68 Other Patients in the Literature.

INTRODUCTION: We came across 3 cases of Balo's concentric sclerosis (BCS). The first of these patients presented to an outside hospital and was transferred to our institution due to complications resulting from a biopsy. The other 2 patients, despite having a characteristic imaging appearance and despite insistence on our part on the diagnosis of BCS, underwent a surgical procedure, which could have been prevented. This led us to review the available literature on BCS. MATERIAL AND METHODS: A total of 68 patients diagnosed with BCS between 1995 and 2015 were studied and the data collected for the clinical presentation and course, imaging, spinal fluid analysis, treatment, and clinical and imaging outcome. CONCLUSIONS: A 25% surgery rate (biopsy or resection) was found in the study. We concluded that this relatively high surgery rate in this auntminnie nonsurgical disease is multifactorial; and includes factors like nonfamiliarity with the disease, anxiety on the part of patients and physicians, due to a sometimes rapidly deteriorating clinical picture; and resemblance of the disease with other entities such as tumor and infection. However, characteristic imaging appearance combined with acute or subacute presentation and dramatic improvement in clinical status after high-dose steroid chemotherapy; are highly suggestive of the disease, and can prevent unnecessary surgery.

Posttraumatic subgaleal herniation of an intracranial cerebral arterial segment.

A rare case of extracranial herniation of an intracranial arterial segment is described in an elderly patient presenting with loss of consciousness following mild head trauma. Cross-sectional imaging of the brain revealed a temporal skull fracture with associated intra-axial and extra-axial bleeding, and a computed tomography angiogram of the head and cerebral digital subtraction angiogram performed a few hours later displayed a rare finding. A small segment of a parietal branch of the right middle cerebral artery (M4 segment) herniated through the skull fracture, which coursed into the extracranial subgaleal space overlying the fracture site, before coursing back into the intracranial compartment. There was no evidence of cerebral ischemia or vascular compromise. The presence of a subgaleal artery on computed tomography angiogram may point to herniation of intracranial artery. In the absence of knowledge of this entity, even basic routine emergency care such as application of a scalp bandage or suturing of a scalp laceration could potentially result in devastating complications of vascular compromise and stroke.

Complete Genome Sequence of Agrobacterium sp. Strain 33MFTa1.1, Isolated from Thlaspi arvense Roots.

Agrobacterium sp. strain 33MFTa1.1 was isolated for functional host-microbe interaction studies from the Thlaspi arvense root-associated microbiome. The complete genome is comprised of a circular chromosome of 2,771,937 bp, a linear chromosome of 2,068,443 bp, and a plasmid of 496,948 bp, with G+C contents of 59%, 59%, and 58%, respectively.

Prevalence of Potentially Clinically Significant Magnetic Resonance Imaging Findings in Athletes with and without Sport-Related Concussion.

Previous studies have shown that mild traumatic brain injury (mTBI) can cause abnormalities in clinically relevant magnetic resonance imaging (MRI) sequences. No large-scale study, however, has prospectively assessed this in athletes with sport-related concussion (SRC). The aim of the current study was to characterize and compare the prevalence of acute, trauma-related MRI findings and clinically significant, non-specific MRI findings in athletes with and without SRC. College and high-school athletes were prospectively enrolled and participated in scanning sessions between January 2015 through August 2017. Concussed contact sport athletes (n = 138; 14 female [F]; 19.5 ± 1.6 years) completed up to four scanning sessions after SRC. Non-concussed contact (n = 135; 15 F; 19.7 ± 1.6) and non-contact athletes (n = 96; 15 F; 20.0 ± 1.7) completed similar scanning sessions and served as controls. Board-certified neuroradiologists, blinded to SRC status, reviewed T1-weighted and T2-weighted fluid-attenuated inversion recovery and T2*-weighted and T2-weighted images for acute (i.e., injury-related) or non-acute findings that prompted recommendation for clinical follow-up. Concussed athletes were more likely to have MRI findings relative to contact (30.4% vs. 15.6%; odds ratio [OR] = 2.32; p = 0.01) and non-contact control athletes (19.8%; OR = 2.11; p = 0.04). Female athletes were more likely to have MRI findings than males (43.2% vs. 19.4%; OR = 2.62; p = 0.01). One athlete with SRC had an acute, injury-related finding; group differences were largely driven by increased rate of non-specific white matter hyperintensities in concussed athletes. This prospective, large-scale study demonstrates that <1% of SRCs are associated with acute injury findings on qualitative structural MRI, providing empirical support for clinical guidelines that do not recommend use of MRI after SRC.

Interobserver Reliability of Magnetic Resonance Imaging Predictors of Outcome in Cervical Spine Degenerative Conditions.

BACKGROUND: Although recent work has focused on characterizing quantitative magnetic resonance imaging (MRI) markers that may predict outcome among patients with cervical degenerative conditions, little is known about their reliability. Measurement and reporting of these markers is time-consuming and nonstandardized, preventing routine use in clinical care. METHODS: We retrospectively analyzed cervical MRI among subjects prospectively enrolled in a health outcomes study of elective surgery for degenerative cervical spine conditions. Two radiologists independently reviewed MRI for presence or absence and length of cord signal change, level of worst cord compression, axial anteroposterior (AP) and lateral spinal cord diameter, midsagittal AP diameter, and kyphosis. Interobserver reliability was compared using kappa and intraclass correlation coefficient (ICC). RESULTS: Inclusion criteria were met by 209 patients who had MRI available for review. Most patients were female (58%) and middle-aged (mean age 51 years), and 54% had a diagnosis of myelopathy. Reliability was fair for cord signal change on T1 (κ = 0.33) and good on T2 (κ = 0.74) images. Among patients with T2 change (n = 22), reliability for signal change length was good (ICC = 0.67). For level of worst compression, reliability was good (κ = 0.79). For AP cord diameter, reliability was very good (ICC = 0.82; T2/midsagittal) and good (ICC = 0.66; T2/axial). Reliability was moderate for lateral cord diameter (ICC = 0.55; T2/axial) and good for kyphosis (κ = 0.76). CONCLUSIONS: Good and very good reliability observed in measuring T2-weighted spinal cord signal change, level of worst compression, AP cord diameter, and kyphosis support use of these markers in standardized reporting, which could be incorporated into routine clinical use.

Genomic features of bacterial adaptation to plants.

Plants intimately associate with diverse bacteria. Plant-associated bacteria have ostensibly evolved genes that enable them to adapt to plant environments. However, the identities of such genes are mostly unknown, and their functions are poorly characterized. We sequenced 484 genomes of bacterial isolates from roots of Brassicaceae, poplar, and maize. We then compared 3,837 bacterial genomes to identify thousands of plant-associated gene clusters. Genomes of plant-associated bacteria encode more carbohydrate metabolism functions and fewer mobile elements than related non-plant-associated genomes do. We experimentally validated candidates from two sets of plant-associated genes: one involved in plant colonization, and the other serving in microbe-microbe competition between plant-associated bacteria. We also identified 64 plant-associated protein domains that potentially mimic plant domains; some are shared with plant-associated fungi and oomycetes. This work expands the genome-based understanding of plant-microbe interactions and provides potential leads for efficient and sustainable agriculture through microbiome engineering.

Multimodality imaging in cranial blastomycosis, a great mimicker: Case-based illustration with review of clinical and imaging findings.

We describe the clinical, laboratory, and imaging data of three patients who are proven cases of blastomycosis with cranial involvement. In this review, we discuss the imaging features of cranial blastomycosis with relevant clinical case examples including computed tomography (CT), magnetic resonance imaging (MRI), and advanced MR imaging techniques like magnetic resonance spectroscopy (MRS) and MR perfusion. Literature is reviewed for modern-day diagnosis and treatment of this fatal intracranial infection, if not diagnosed promptly and managed effectively.

Cortical and Subcortical Substrates of Cranial Nerve Function.

The pivotal role of cranial nerves in a wholesome life experience cannot be overemphasized. Research has opened new avenues to understand cranial nerve function. Classical concept of strict bilateral cortical control of cranial nerves has given way to concepts of hemispheric dominance and hemispheric lateralization. An astute Neuroradiologist should keep abreast of these concepts and help patients and referring physicians by applying this knowledge in reading images. This chapter provides an overview of cranial nerve function and latest concepts pertaining to their cortical and subcortical control.

Functional and Dysfunctional Sensorimotor Anatomy and Imaging.

The sensorimotor system of the human brain and body is fundamental only in its central role in our daily lives. On further examination, it is a system with intricate and complex anatomical, physiological, and functional relationships. Sensorimotor areas including primary sensorimotor, premotor, supplementary motor, and higher order somatosensory cortices are critical for function and can be localized at routine neuroimaging with a familiarity of sulcal and gyral landmarks. Likewise, a thorough understanding of the functions and dysfunctions of these areas can empower the neuroradiologist and lead to superior imaging search patterns, diagnostic considerations, and patient care recommendations in daily clinical practice. Presurgical functional brain mapping of the sensorimotor system may be necessary in scenarios with distortion of anatomical landmarks, multiplanar localization, homunculus localization, congenital brain anomalies, informing diffusion tensor imaging interpretations, and localizing nonvisible targets.

Imaging of Cortical and White Matter Language Processing.

Although investigations into the functional and anatomical organization of language within the human brain began centuries ago, it is recent advanced imaging techniques including functional magnetic resonance imaging and diffusion tensor imaging that have helped propel our understanding forward at an unprecedented rate. Important cortical brain regions and white matter tracts in language processing subsystems including semantic, phonological, and orthographic functions have been identified. An understanding of functional and dysfunctional language anatomy is critical for practicing radiologists. This knowledge can be applied to routine neuroimaging examinations as well as to more advanced examinations such as presurgical brain mapping.

Preoperative diffusion tensor imaging: improving neurosurgical outcomes in brain tumor patients.

Preoperative mapping has revolutionized neurosurgical care for brain tumor patients. Maximizing resections has improved diagnosis, optimized treatment algorithms, and decreased potentially devastating postoperative deficits. Although mapping has multiple steps and complimentary localization sources, diffusion tensor imaging (DTI) excels in its essential role in depicting white matter tracts. A thorough understanding of DTI, data visualization methods, and limitations with mastery of functional and dysfunctional white matter anatomy is necessary to realize the potential of DTI. By establishing spatial relationships between lesion borders and functional networks preoperatively and intraoperatively, DTI is central to high-risk neurosurgical resections and becoming the standard of care.