The speech neuroprosthesis.

Loss of speech after paralysis is devastating, but circumventing motor-pathway injury by directly decoding speech from intact cortical activity has the potential to restore natural communication and self-expression. Recent discoveries have defined how key features of speech production are facilitated by the coordinated activity of vocal-tract articulatory and motor-planning cortical representations. In this Review, we highlight such progress and how it has led to successful speech decoding, first in individuals implanted with intracranial electrodes for clinical epilepsy monitoring and subsequently in individuals with paralysis as part of early feasibility clinical trials to restore speech. We discuss high-spatiotemporal-resolution neural interfaces and the adaptation of state-of-the-art speech computational algorithms that have driven rapid and substantial progress in decoding neural activity into text, audible speech, and facial movements. Although restoring natural speech is a long-term goal, speech neuroprostheses already have performance levels that surpass communication rates offered by current assistive-communication technology. Given this accelerated rate of progress in the field, we propose key evaluation metrics for speed and accuracy, among others, to help standardize across studies. We finish by highlighting several directions to more fully explore the multidimensional feature space of speech and language, which will continue to accelerate progress towards a clinically viable speech neuroprosthesis.

A bilingual speech neuroprosthesis driven by cortical articulatory representations shared between languages.

Advancements in decoding speech from brain activity have focused on decoding a single language. Hence, the extent to which bilingual speech production relies on unique or shared cortical activity across languages has remained unclear. Here, we leveraged electrocorticography, along with deep-learning and statistical natural-language models of English and Spanish, to record and decode activity from speech-motor cortex of a Spanish-English bilingual with vocal-tract and limb paralysis into sentences in either language. This was achieved without requiring the participant to manually specify the target language. Decoding models relied on shared vocal-tract articulatory representations across languages, which allowed us to build a syllable classifier that generalized across a shared set of English and Spanish syllables. Transfer learning expedited training of the bilingual decoder by enabling neural data recorded in one language to improve decoding in the other language. Overall, our findings suggest shared cortical articulatory representations that persist after paralysis and enable the decoding of multiple languages without the need to train separate language-specific decoders.

Intraoperative cortical stimulation mapping with laryngeal electromyography for the localization of human laryngeal motor cortex.

OBJECTIVE: The objectives of this study were to describe the authors' clinical methodology and outcomes for mapping the laryngeal motor cortex (LMC) and define localization of the LMC in a cohort of neurosurgical patients undergoing intraoperative brain mapping. Because of mapping variability across patients, the authors aimed to define the probabilistic distribution of cortical sites that evoke laryngeal movement, as well as adjacent cortical somatotopic representations for the face (mouth), tongue, and hand. METHODS: Thirty-six patients underwent left (n = 18) or right (n = 18) craniotomy with asleep motor mapping. For each patient, electromyography (EMG) electrodes were placed in the face, tongue, and hand; a nerve integrity monitor (NIM) endotracheal tube with surface electrodes detected EMG activity from the bilateral vocal folds. After dense cortical stimulation was delivered throughout the sensorimotor cortex, motor responses were then mapped onto a three-dimensional reconstruction of the patient's cortical surfaces for location characterization of the evoked responses. Finally, stimulation sites were transformed into a two-dimensional coordinate system for probabilistic mapping of the stimulation site relative to the central sulcus and sylvian fissure. RESULTS: The authors found that the LMC was predominantly localized to a mid precentral gyrus region, dorsal to face representation and surrounding a transverse sulcus ventral to the hand knob. In 14 of 36 patients, the authors identified additional laryngeal responses located ventral to all orofacial representations, providing evidence for dual LMC representations. CONCLUSIONS: The authors determined the probabilistic distribution of the LMC. Cortical stimulation mapping with an NIM endotracheal tube is an easy and effective method for mapping the LMC and is simply integrated into the current neuromonitoring methods for brain mapping.

Interictal epileptiform discharges contribute to word-finding difficulty in epilepsy through multiple cognitive mechanisms.

OBJECTIVE: Cognitive impairment often impacts quality of life in epilepsy even if seizures are controlled. Word-finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word-finding difficulty in patients, and if so, through which cognitive mechanism(s). METHODS: Twenty-three patients undergoing intracranial monitoring for drug-resistant epilepsy participated in multiple tasks involving word production (auditory naming, short-term verbal free recall, repetition) to probe word-finding difficulty across different cognitive domains. We compared behavioral performance between trials with versus without interictal discharges across six major brain areas and adjusted for intersubject differences using mixed-effects models. We also evaluated for subjective word-finding difficulties through retrospective chart review. RESULTS: Subjective word-finding difficulty was reported by the majority (79%) of studied patients preoperatively. During intracranial recordings, interictal epileptiform discharges (IEDs) in the medial temporal lobe were associated with long-term lexicosemantic memory impairments as indexed by auditory naming (p = .009), in addition to their established impact on short-term verbal memory as indexed by free recall (p = .004). Interictal discharges involving the lateral temporal cortex and lateral frontal cortex were associated with delayed reaction time in the auditory naming task (p = .016 and p = .018), as well as phonological working memory impairments as indexed by repetition reaction time (p = .002). Effects of IEDs across anatomical regions were strongly dependent on their precise timing within the task. SIGNIFICANCE: IEDs appear to act through multiple cognitive mechanisms to form a convergent basis for the debilitating clinical word-finding difficulty reported by patients with epilepsy. This was particularly notable for medial temporal spikes, which are quite common in adult focal epilepsy. In parallel with the treatment of seizures, the modulation of interictal discharges through emerging pharmacological means and neurostimulation approaches may be an opportunity to help address devastating memory and language impairments in epilepsy.

Genetic bases of resistance to the rice hoja blanca disease deciphered by a quantitative trait locus approach.

Rice hoja blanca (RHB) is one of the most serious diseases in rice-growing areas in tropical Americas. Its causal agent is RHB virus (RHBV), transmitted by the planthopper Tagosodes orizicolus Müir. Genetic resistance is the most effective and environment-friendly way of controlling the disease. So far, only 1 major quantitative trait locus (QTL) of Oryza sativa ssp. japonica origin, qHBV4.1, that alters the incidence of the virus symptoms in 2 Colombian cultivars has been reported. This resistance has already started to be broken, stressing the urgent need for diversifying the resistance sources. In the present study, we performed a search for new QTLs of O. sativa indica origin associated with RHB resistance. We used 4 F2:3-segregating populations derived from indica-resistant varieties crossed with a highly susceptible japonica pivot parent. Besides the standard method for measuring disease incidence, we developed a new method based on computer-assisted image processing to determine the affected leaf area (ALA) as a measure of symptom severity. Based on the disease severity and incidence scores in the F3 families under greenhouse conditions and SNP genotyping of the F2 individuals, we identified 4 new indica QTLs for RHB resistance on rice chromosomes 4, 6, and 11, namely, qHBV4.2WAS208, qHBV6.1PTB25, qHBV11.1, and qHBV11.2, respectively. We also confirmed the wide-range action of qHBV4.1. Among the 5 QTLs, qHBV4.1 and qHBV11.1 had the largest effects on incidence and severity, respectively. These results provide a more complete understanding of the genetic bases of RHBV resistance in the cultivated rice gene pool and can be used to develop marker-aided breeding strategies to improve RHB resistance. The power of joint- and meta-analyses allowed precise mapping and candidate gene identification, providing the basis for positional cloning of the 2 major QTLs qHBV4.1 and qHBV11.1.

A high-performance neuroprosthesis for speech decoding and avatar control.

Speech neuroprostheses have the potential to restore communication to people living with paralysis, but naturalistic speed and expressivity are elusive1. Here we use high-density surface recordings of the speech cortex in a clinical-trial participant with severe limb and vocal paralysis to achieve high-performance real-time decoding across three complementary speech-related output modalities: text, speech audio and facial-avatar animation. We trained and evaluated deep-learning models using neural data collected as the participant attempted to silently speak sentences. For text, we demonstrate accurate and rapid large-vocabulary decoding with a median rate of 78 words per minute and median word error rate of 25%. For speech audio, we demonstrate intelligible and rapid speech synthesis and personalization to the participant's pre-injury voice. For facial-avatar animation, we demonstrate the control of virtual orofacial movements for speech and non-speech communicative gestures. The decoders reached high performance with less than two weeks of training. Our findings introduce a multimodal speech-neuroprosthetic approach that has substantial promise to restore full, embodied communication to people living with severe paralysis.

Rescue of Alzheimer's disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells.

Alzheimer's disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD phenotype in 5xFAD mice and that transplantation may prevent microglia activation. Indeed, complete prevention of memory loss and neurocognitive impairment and decrease of ß-amyloid plaques in the hippocampus and cortex were observed in the WT HSPC-transplanted 5xFAD mice compared with untreated 5xFAD mice and with mice transplanted with 5xFAD HSPCs. Neuroinflammation was also significantly reduced. Transcriptomic analysis revealed a significant decrease in gene expression related to "disease-associated microglia" in the cortex and "neurodegeneration-associated endothelial cells" in the hippocampus of the WT HSPC-transplanted 5xFAD mice compared with diseased controls. This work shows that HSPC transplant has the potential to prevent AD-associated complications and represents a promising therapeutic avenue for this disease.

A Systematic Review Comparing Focused Ultrasound Surgery With Radiosurgery for Essential Tremor.

BACKGROUND: Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared. OBJECTIVE: To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET. METHODS: We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence. RESULTS: Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: -11.6 (95% CI: -13.3, -9.9); SRS-T: -10.3 (95% CI: -14.2, -6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume. CONCLUSION: Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.

Apraxia of speech with phonological alexia and agraphia following resection of the left middle precentral gyrus: illustrative case.

BACKGROUND: Apraxia of speech is a disorder of speech-motor planning in which articulation is effortful and error-prone despite normal strength of the articulators. Phonological alexia and agraphia are disorders of reading and writing disproportionately affecting unfamiliar words. These disorders are almost always accompanied by aphasia. OBSERVATIONS: A 36-year-old woman underwent resection of a grade IV astrocytoma based in the left middle precentral gyrus, including a cortical site associated with speech arrest during electrocortical stimulation mapping. Following surgery, she exhibited moderate apraxia of speech and difficulty with reading and spelling, both of which improved but persisted 6 months after surgery. A battery of speech and language assessments was administered, revealing preserved comprehension, naming, cognition, and orofacial praxis, with largely isolated deficits in speech-motor planning and the spelling and reading of nonwords. LESSONS: This case describes a specific constellation of speech-motor and written language symptoms-apraxia of speech, phonological agraphia, and phonological alexia in the absence of aphasia-which the authors theorize may be attributable to disruption of a single process of "motor-phonological sequencing." The middle precentral gyrus may play an important role in the planning of motorically complex phonological sequences for production, independent of output modality.

TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells.

Neutrophil extracellular traps (NETs) have been implicated in several hallmarks of cancer. Among the protumor effects, NETs promote epithelial-mesenchymal transition (EMT) in different cancer models. EMT has been linked to an enhanced expression of the clotting-initiating protein, tissue factor (TF), thus favoring the metastatic potential. TF may also exert protumor effects by facilitating the activation of protease-activated receptor 2 (PAR2). Herein, we evaluated whether NETs could induce TF expression in breast cancer cells and further promote procoagulant and intracellular signaling effects via the TF/PAR2 axis. T-47D and MCF7 cell lines were treated with isolated NETs, and samples were obtained for real-time PCR, flow cytometry, Western blotting, and plasma coagulation assays. In silico analyses were performed employing RNA-seq data from breast cancer patients deposited in The Cancer Genome Atlas (TCGA) database. A positive correlation was observed between neutrophil/NETs gene signatures and TF gene expression. Neutrophils/NETs gene signatures and PAR2 gene expression also showed a significant positive correlation in the bioinformatics model. In vitro analysis showed that treatment with NETs upregulated TF gene and protein expression in breast cancer cell lines. The inhibition of ERK/JNK reduced the TF gene expression induced by NETs. Remarkably, the pharmacological or genetic inhibition of the TF/PAR2 signaling axis attenuated the NETs-induced expression of several protumor genes. Also, treatment of NETs with a neutrophil elastase inhibitor reduced the expression of metastasis-related genes. Our results suggest that the TF/PAR2 signaling axis contributes to the pro-cancer effects of NETs in human breast cancer cells.

A Neurosurgical Functional Dissection of the Middle Precentral Gyrus during Speech Production.

Classical models have traditionally focused on the left posterior inferior frontal gyrus (Broca's area) as a key region for motor planning of speech production. However, converging evidence suggests that it is not critical for either speech motor planning or execution. Alternative cortical areas supporting high-level speech motor planning have yet to be defined. In this review, we focus on the precentral gyrus, whose role in speech production is often thought to be limited to lower-level articulatory muscle control. In particular, we highlight neurosurgical investigations that have shed light on a cortical region anatomically located near the midpoint of the precentral gyrus, hence called the middle precentral gyrus (midPrCG). The midPrCG is functionally located between dorsal hand and ventral orofacial cortical representations and exhibits unique sensorimotor and multisensory functions relevant for speech processing. This includes motor control of the larynx, auditory processing, as well as a role in reading and writing. Furthermore, direct electrical stimulation of midPrCG can evoke complex movements, such as vocalization, and selective injury can cause deficits in verbal fluency, such as pure apraxia of speech. Based on these findings, we propose that midPrCG is essential to phonological-motoric aspects of speech production, especially syllabic-level speech sequencing, a role traditionally ascribed to Broca's area. The midPrCG is a cortical brain area that should be included in contemporary models of speech production with a unique role in speech motor planning and execution.

Ventral Intermediate Nucleus of the Thalamus versus Posterior Subthalamic Area: Network Meta-Analysis of DBS Target Site Efficacy for Essential Tremor.

BACKGROUND: Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (Vim) of the thalamus or the posterior subthalamic area (PSA) are effective treatments for essential tremor (ET). However, their relative efficacy is unknown. OBJECTIVE: Here, we present the first systematic review and network meta-analysis, examining the efficacy of Vim versus PSA DBS for treating medically refractory ET. METHODS: We included all primary studies that reported validated Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores pre-/postimplantation or on-/off-stimulation postimplantation, for patients receiving either Vim or PSA DBS. The primary outcome was FTM-TRS score reduction; the secondary outcome was percent reduction in score. We categorized all outcomes as short-term (≤12 months) or long-term (>12 months). RESULTS: For pre-/postimplantation comparisons, 19 and 11 studies met inclusion criteria for short- and long-term follow-ups, respectively. For on-/off-stimulation tremor score comparisons, 8 studies met inclusion criteria for short-term follow-up. Network meta-analysis of pre-/postimplantation tremor scores showed greater tremor reduction with PSA implantation short-term (absolute tremor reduction: PSA: -30.94 [95% confidence interval (CI): -34.93, -26.95]; Vim: -26.26 [95% CI: -33.39, -19.12]; relative tremor reduction: PSA: 63.3% [95% CI: 61.8%-64.8%]; Vim: 57.8% [95% CI: 56.5%-59.0%]). However, there was no difference in efficacy between PSA and Vim DBS when comparing tremor on-versus off-stimulation at short-term follow-up or pre- versus postimplantation tremor reduction long-term. CONCLUSION: Our systematic review highlighted both heterogeneity in scoring systems used and lack of transparency in reporting total scores, limiting direct comparison across studies. We found a modestly superior efficacy with PSA stimulation in the short term, but no difference in tremor reduction long-term.

A framework For brain atlases: Lessons from seizure dynamics.

Brain maps, or atlases, are essential tools for studying brain function and organization. The abundance of available atlases used across the neuroscience literature, however, creates an implicit challenge that may alter the hypotheses and predictions we make about neurological function and pathophysiology. Here, we demonstrate how parcellation scale, shape, anatomical coverage, and other atlas features may impact our prediction of the brain's function from its underlying structure. We show how network topology, structure-function correlation (SFC), and the power to test specific hypotheses about epilepsy pathophysiology may change as a result of atlas choice and atlas features. Through the lens of our disease system, we propose a general framework and algorithm for atlas selection. This framework aims to maximize the descriptive, explanatory, and predictive validity of an atlas. Broadly, our framework strives to provide empirical guidance to neuroscience research utilizing the various atlases published over the last century.

Collateral Arteriogenesis Involves a Sympathetic Denervation That Is Associated With Abnormal α-Adrenergic Signaling and a Transient Loss of Vascular Tone.

Stimulating collateral arteriogenesis is an attractive therapeutic target for peripheral artery disease (PAD). However, the potency of arteriogenesis-stimulation in animal models has not been matched with efficacy in clinical trials. This may be because the presence of enlarged collaterals is not sufficient to relieve symptoms of PAD, suggesting that collateral function is also important. Specifically, collaterals are the primary site of vascular resistance following arterial occlusion, and impaired collateral vasodilation could impact downstream tissue perfusion and limb function. Therefore, we evaluated the effects of arteriogenesis on collateral vascular reactivity. Following femoral artery ligation in the mouse hindlimb, collateral functional vasodilation was impaired at day 7 (17 ± 3 vs. 60 ± 8%) but restored by day 28. This impairment was due to a high resting diameter (73 ± 4 µm at rest vs. 84 ± 3 µm dilated), which does not appear to be a beneficial effect of arteriogenesis because increasing tissue metabolic demand through voluntary exercise decreased resting diameter and restored vascular reactivity at day 7. The high diameter in sedentary animals was not due to sustained NO-dependent vasodilation or defective myogenic constriction, as there were no differences between the enlarged and native collaterals in response to eNOS inhibition with L-NAME or L-type calcium channel inhibition with nifedipine, respectively. Surprisingly, in the context of reduced vascular tone, vasoconstriction in response to the α-adrenergic agonist norepinephrine was enhanced in the enlarged collateral (-62 ± 2 vs. -37 ± 2%) while vasodilation in response to the α-adrenergic antagonist prazosin was reduced (6 ± 4% vs. 22 ± 16%), indicating a lack of α-adrenergic receptor activation by endogenous norepinephrine and suggesting a denervation of the neuroeffector junction. Staining for tyrosine hydroxylase demonstrated sympathetic denervation, with neurons occupying less area and located further from the enlarged collateral at day 7. Inversely, MMP2 presence surrounding the enlarged collateral was greater at day 7, suggesting that denervation may be related to extracellular matrix degradation during arteriogenesis. Further investigation on vascular wall maturation and the functionality of enlarged collaterals holds promise for identifying novel therapeutic targets to enhance arteriogenesis in patients with PAD.

Effects of anterior thalamic nuclei stimulation on hippocampal activity: Chronic recording in a patient with drug-resistant focal epilepsy.

Implanted neurostimulation devices are gaining traction as palliative treatment options for certain forms of drug-resistant epilepsy, but clinical utility of these devices is hindered by incomplete mechanistic understanding of their therapeutic effects. Approved devices for anterior thalamic nuclei deep brain stimulation (ANT DBS) are thought to work at a network level, but limited sensing capability precludes characterization of neurophysiological effects outside the thalamus. Here, we describe a patient with drug-resistant temporal lobe epilepsy who was implanted with a responsive neurostimulation device (RNS System), involving hippocampal and ipsilateral temporal neocortical leads, and subsequently received ANT DBS. Over 1.5 years, RNS System electrocorticography enabled multiscale characterization of neurophysiological effects of thalamic stimulation. In brain regions sampled by the RNS System, ANT DBS produced acute, phasic, frequency-dependent responses, including suppression of hippocampal low frequency local field potentials. ANT DBS modulated functional connectivity between hippocampus and neocortex. Finally, ANT DBS progressively suppressed hippocampal epileptiform activity in relation to the extent of hippocampal theta suppression, which informs stimulation parameter selection for ANT DBS. Taken together, this unique clinical scenario, involving hippocampal recordings of unprecedented chronicity alongside ANT DBS, sheds light on the therapeutic mechanism of thalamic stimulation and highlights capabilities needed in next-generation devices.

Empathy, well-being, and mental health: do gender differences diminish by the end of medical school?

This study aims to investigate if medical students demonstrate differences related to gender in terms of empathy, burnout, tolerance, openness to spirituality, well-being, and mental health, and to examine whether these differences vary across levels of medical training. A cross-sectional study was conducted in the first semester of 2015 in a Brazilian medical school. The following were evaluated: quality of life (WHOQOL-Bref), burnout (Oldenburg), mental health (DASS-21), empathy (Empathy Inventory and ESWIM), and tolerance, well-being, and openness to spirituality (ESWIM). We investigated how these outcomes varied in terms of gender, stage of medical training, and its interaction using a two-way MANOVA. A total of 776 students were included and important differences were observed. As medical training advanced, the differences between genders that were present during students' initial years (greater empathy, worse quality of life, and worse mental health among women) tended to become nonsignificant during the clerkship years. In addition, a significant interaction between stage and gender was found for ESWIM Wellness; WHOQOL; DASS Anxiety and DASS Stress. These results may denote a shortcoming in the way medical schools approach gender differences. Educators should consider these findings when restructuring curricula to respect gender differences, thus fostering their respective potentials.

GSTP1 rs1695 and rs1871042, and SOD2 rs4880 as molecular markers of lipid peroxidation in blood storage.

BACKGROUND: Red blood cells (RBC) are subject to oxidative stress by reactive oxygen species (ROS) during storage. Molecular characterisation of oxidative stress in stored RBC, which may also occur in other blood components during long periods of storage, is rare. MATERIALS AND METHODS: Our study included 45 healthy RBC donors recruited in Brazil. Blood was collected into standard Grifols® Triple Bags containing CPD SAG-M. Haematological values, biochemical data, and oxidative stress markers were assessed weekly during storage until 42 days after collection. GSTM1 and GSTT1 were determined by multiplex-polymerase chain reaction (PCR), while GSTP1 rs1695 and rs1871042, CAT rs1001179, and SOD2 rs4880 were evaluated by real-time PCR. RESULTS: A direct proportional relationship was found between storage time and levels of ROS and thiobarbituric acid reactive substances (TBARS, indicators of lipid peroxidation) (p<0.001). These parameters were indirectly proportional to ABTS values (p<0.001). The plasma concentration of TBARS was associated with GSTP1 303AG/GG, GSTP1 -16CT/TT, and SOD2 47CT/TT genotypes. Single-nucleotide polymorphisms at the CAT C-262T gene were not associated with TBARS, nor were oxidative markers of ROS. DISCUSSION: Prolonged storage may result in the onset of erythrocyte deterioration. Our results clearly indicate that erythrocytes are capable of attenuating ROS for 2 weeks of storage. We observed an association between elevated TBARS levels and the presence of GSTP1 and SOD2 variants in stored RBC. Although notable for heterozygous variants, this association was even stronger for the homozygous variants GSTP1 rs1695 (303GG), GSTP1 rs1871042 (-16TT), and SOD2 rs4880 (47TT). These findings accentuate the importance of genetic factors in storage lesions and will expand our understanding and consideration of endogenous and exogenous causes in improving clinical treatment with blood transfusions.

Rhamnose in plants - from biosynthesis to diverse functions.

In plants, the deoxy sugar l-rhamnose is widely present as rhamnose-containing polymers in cell walls and as part of the decoration of various specialized metabolites. Here, we review the current knowledge on the distribution of rhamnose, highlighting the differences between what is known in dicotyledoneuos compared to commelinid monocotyledoneous (grasses) plants. We discuss the biosynthesis and transport of UDP-rhamnose, as well as the transfer of rhamnose from UDP-rhamnose to various primary and specialized metabolites. This is carried out by rhamnosyltransferases, enzymes that can use a large variety of substrates. Some unique characteristics of rhamnose synthases, the multifunctional enzymes responsible for the conversion of UDP-glucose into UDP-rhamnose, are considered, particularly from the perspective of their ability to convert glucose present in flavonoids. Finally, we discuss how little is still known with regards to how plants rescue rhamnose from the many compounds to which it is linked, or how rhamnose is catabolized.

Radioprotective garment-inspired biodegradable polymetal nanoparticles for enhanced CT contrast production.

Numerous formulations of nanoparticle-based X-ray computed tomography (CT) contrast agents made of heavy metal elements are under investigation for their ability to provide improved CT imaging. Thus far, most experimental nanoparticle-based CT contrast agents have been developed with atoms of a single element. However, inspired by the composites formed from multiple elements used in radioprotective garments, we hypothesized that contrast agents made of several elements whose K-edge energies are spaced out in the high photon flux region could achieve high, broadband X-ray attenuation across the energies used in X-ray source spectra. Herein, we synthesized sub-5 nm core inorganic nanoparticles containing gold, tantalum, and cerium, and encapsulated them in polymeric nanoparticles to form polymetal nanoparticles (PMNP). We found that PMNP with multiple payload elements generate higher and more stable CT contrast than contrast agents made from a single contrast generating material, demonstrating the potential benefits of incorporating multiple suitable elements as CT contrast payloads.