Recording advances for neural prosthetics

An important challenge for neural prosthetics research is to record from populations of neurons over long periods of time, ideally for the lifetime of the patient. Two new advances toward this goal are described, the use of local field potentials (LFPs) and autonomously positioned recording electrodes. LFPs are the composite extracellular potential field from several hundreds of neurons around the electrode tip. LFP recordings can be maintained for longer periods of time than single cell recordings. We find that similar information can be decoded from LFP and spike recordings, with better performance for state decodes with LFPs and, depending on the area, equivalent or slightly less than equivalent performance for signaling the direction of planned movements. Movable electrodes in microdrives can be adjusted in the tissue to optimize recordings, but their movements must be automated to be a practical benefit to patients. We have developed automation algorithms and a meso-scale autonomous electrode testbed, and demonstrated that this system can autonomously isolate and maintain the recorded signal quality of single cells in the cortex of awake, behaving monkeys. These two advances show promise for developing very long term recording for neural prosthetic applications

Leaf-applied sodium chloride promotes cadmium accumulation in durum wheat grain

Cadmium (Cd) accumulation in durum wheat grain is a growing concern. Among the factors affecting Cd accumulation in plants, soil chloride (Cl) concentration plays a critical role. The effect of leaf NaCl application on grain Cd was studied in greenhouse-grown durum wheat (Triticum turgidum L. durum, cv. Balcali-2000) by immersing (10 s) intact flag leaves into Cd and/or NaCl-containing solutions for 14 times during heading and dough stages. Immersing flag leaves in solutions containing increasing amount of Cd resulted in substantial increases in grain Cd concentration. Adding NaCl alone or in combination with the Cd-containing immersion solution promoted accumulation of Cd in the grains, by up to 41%. In contrast, Zn concentrations of grains were not affected or even decreased by the NaCl treatments. This is likely due to the effect of Cl complexing Cd and reducing positive charge on the metal ion, an effect that is much smaller for Zn. Charge reduction or removal (CdCl2 0 species) would increase the diffusivity/lipophilicity of Cd and enhance its capability to penetrate the leaf epidermis and across membranes. Of even more significance to human health was the ability of Cl alone to penetrate leaf tissue and mobilize and enhance shoot Cd transfer to grains, yet reducing or not affecting Zn transfer

Preparation of Butadienylpyridines by Iridium-NHC-Catalyzed Alkyne Hydroalkenylation and Quinolizine Rearrangement

Iridium(I) N-heterocyclic carbene complexes of formula Ir(¿2O, O’-BHetA)(IPr)(¿2-coe) [BHetA=bis-heteroatomic acidato, acetylacetonate or acetate; IPr=1, 3-bis(2, 6-diisopropylphenyl)imidazolin-2-carbene; coe=cyclooctene] have been prepared by treating Ir(¿2O, O’-BHetA)(¿2-coe)2 complexes with IPr. These complexes react with 2-vinylpyridine to afford the hydrido-iridium(III)-alkenyl cyclometalated derivatives IrH(¿2O, O’-BHetA)(¿2N, C-C7H6N)(IPr) through the iridium(I) intermediate Ir(¿2O, O’-BHetA)(IPr)(¿2-C7H7N). The cyclometalated IrH(¿2O, O’-acac)(¿2N, C–C7H6N)(IPr) complex efficiently catalyzes the hydroalkenylation of aromatic and aliphatic terminal alkynes and enynes with 2-vinylpyridine to afford 2-(4R-butadienyl)pyridines with Z, E configuration as the major reaction products (yield up to 89 %). In addition, unprecedented (Z)-2-butadienyl-5R-pyridine derivatives have been obtained as minor reaction products (yield up to 21 %) from the elusive 1Z, 3gem-butadienyl hydroalkenylation products. These compounds undergo a thermal 6p-electrocyclization to afford bicyclic 4H-quinolizine derivatives that, under catalytic reaction conditions, tautomerize to 6H-quinolizine to afford the (Z)-2-(butadienyl)-5R-pyridine by a retro-electrocyclization reaction. © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH Gmb

Kidney and Colon Electrolyte Transport in CHIF Knockout Mice

Corticosteroid hormone induced factor (CHIF) is a small epithelial-specific protein regulated by aldosterone and K+ intake. It is a member of the FXYD family of single span transmembrane proteins involved in the regulation of ion transport. Recent data have suggested that CHIF interacts with the a subunit of the Na+-K+-ATPase and increases the pump's affinity to cell Na+. CHIF knockout (KO) mice have mild renal phenotype under low Na+ or high K+ diets. The present study further characterizes kidney electrolyte metabolism in CHIF KO mice and describes abnormalities in the colonic ion transport function. Kidney: KO mice were not compromised in salt and water balance under resting conditions. Fractional excretions (FE) of Na+ and K+ were normal and the animals had no deficit in the adaptation to low Na+ or high K+ intake. Glucocorticoid treatment did not unmask any difference. The effects of amiloride on Na+ absorption were not different at any treatment protocol. In contrast, FEK+ was reduced by 35% in KO mice under low Na+ intake. COLON: Amiloride inhibitable Na+ absorption was reduced in distal colon by 42%, 54% and 58% under control conditions, glucocorticoid treatment and low Na+ intake, respectively. Also, the cAMP dependent ion transport was significantly diminished. Forskolin induced equivalent short circuit current (I'SC) was reduced by 41%, 32% and 58%, under control conditions, high K+, and low Na+ intake, respectively. The present findings support a role of CHIF as an indirect modulator of several different ion transport mechanisms and are consistent with regulation of the Na+-K+-ATPase as the common denominator

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

Transcriptome and genome sequencing uncovers functional variation in humans

Summary Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project – the first uniformly processed RNA-seq data from multiple human populations with high-quality genome sequences. We discovered extremely widespread genetic variation affecting regulation of the majority of genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on cellular mechanisms of regulatory and loss-of-function variation, and allowed us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome

Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets

Human-mediated biological exchange has had global social and ecological impacts. In subS-aharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation

Evolution and genetic architecture of sex-limited polymorphism in cuckoos

Sex-limited polymorphism has evolved in many species including our own. Yet, we lack a detailed understanding of the underlying genetic variation and evolutionary processes at work. The brood parasitic common cuckoo (Cuculus canorus) is a prime example of female-limited color polymorphism, where adult males are monochromatic gray and females exhibit either gray or rufous plumage. This polymorphism has been hypothesized to be governed by negative frequency-dependent selection whereby the rarer female morph is protected against harassment by males or from mobbing by parasitized host species. Here, we show that female plumage dichromatism maps to the female-restricted genome. We further demonstrate that, consistent with balancing selection, ancestry of the rufous phenotype is shared with the likewise female dichromatic sister species, the oriental cuckoo (Cuculus optatus). This study shows that sex-specific polymorphism in trait variation can be resolved by genetic variation residing on a sex-limited chromosome and be maintained across species boundaries

Mn bioavailability by polarized Caco-2 cells: comparison between Mn gluconate and Mn oxyprolinate

<p>Abstract</p> <p>Background</p> <p>Micronutrient inadequate intake is responsible of pathological deficiencies and there is a need of assessing the effectiveness of metal supplementation, frequently proposed to rebalance poor diets. Manganese (Mn) is present in many enzymatic intracellular systems crucial for the regulation of cell metabolism, and is contained in commercially available metal supplements.</p> <p>Methods</p> <p>We compared the effects of two different commercial Mn forms, gluconate (MnGluc) and oxyprolinate (MnOxP). For this purpose we used the polarized Caco-2 cells cultured on transwell filters, an established in vitro model of intestinal epithelium. Since micronutrient deficiency may accelerate mitochondrial efficiency, the mitochondrial response of these cells, in the presence of MnGluc and MnOxP, by microscopy methods and by ATP luminescence assay was used.</p> <p>Results</p> <p>In the presence of both MnOxP and MnGluc a sustained mitochondrial activity was shown by mitoTraker labeling (indicative of mitochondrial respiration), but ATP intracellular content remained comparable to untreated cells only in the presence of MnOxP. In addition MnOxP transiently up-regulated the antioxidant enzyme Mn superoxide dismutase more efficiently than MnGluc. Both metal treatments preserved NADH and βNADPH diaphorase oxidative activity, avoided mitochondrial dysfunction, as assessed by the absence of a sustained phosphoERK activation, and were able to maintain cell viability.</p> <p>Conclusions</p> <p>Collectively, our data indicate that MnOxP and MnGluc, and primarily the former, produce a moderate and safe modification of Caco-2 cell metabolism, by activating positive enzymatic mechanisms, thus could contribute to long-term maintenance of cell homeostasis.</p