Reconciling Conflicting Phylogenies in the Origin of Sweet Potato and Dispersal to Polynesia

The sweet potato is one of the world’s most widely consumed crops, yet its evolutionary history is poorly understood. In this paper, we present a comprehensive phylogenetic study of all species closely related to the sweet potato and address several questions pertaining to the sweet potato that remained unanswered. Our research combined genome skimming and target DNA capture to sequence whole chloroplasts and 605 single-copy nuclear regions from 199 specimens representing the sweet potato and all of its crop wild relatives (CWRs). We present strongly supported nuclear and chloroplast phylogenies demonstrating that the sweet potato had an autopolyploid origin and that Ipomoea trifida is its closest relative, confirming that no other extant species were involved in its origin. Phylogenetic analysis of nuclear and chloroplast genomes shows conflicting topologies regarding the monophyly of the sweet potato. The process of chloroplast capture explains these conflicting patterns, showing that I. trifida had a dual role in the origin of the sweet potato, first as its progenitor and second as the species with which the sweet potato introgressed so one of its lineages could capture an I. trifida chloroplast. In addition, we provide evidence that the sweet potato was present in Polynesia in pre-human times. This, together with several other examples of long-distance dispersal in Ipomoea, negates the need to invoke ancient human-mediated transport as an explanation for its presence in Polynesia. These results have important implications for understanding the origin and evolution of a major global food crop and question the existence of pre-Columbian contacts between Polynesia and the American continent

Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component

Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud \ud Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud \ud Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection

Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study

Background: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents. Methods: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data. Findings: Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9–5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1–17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patients vs 1 [<1%] of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 [80%] of 25 patients vs six [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patients vs 12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group). Interpretation: This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes. Funding: UK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Eye-controlled, power wheelchair performs well for ALS patients.

BACKGROUND: Our pilot study tested the feasibility and performance of an eye-controlled power wheelchair for amyotrophic lateral sclerosis (ALS) patients. METHODS: In this prospective pilot study, participants drove the wheelchair three times around an indoor course. We assessed the time to complete the course; starting and stopping on command; turning 90, 135, and 180 degrees; time to backup; and obstacle negotiation. Following their use of the wheelchair, subjects were given a questionnaire to assess user experience. RESULTS: Twelve patients participated, and all were able to complete three trials without difficulty. Eight participants completed all of the individual tasks (eg, turning, stopping, etc.) without any errors. Overall performance ratings were high across all participants (4.6/5-excellent). CONCLUSIONS: Our eye-controlled power wheelchair prototype is feasible and has a very favorable user experience. This system has the potential to improve the mobility and independence of ALS patients, and other groups with motor impairments

The <i>C. elegans</i> cGMP-Dependent Protein Kinase EGL-4 Regulates Nociceptive Behavioral Sensitivity

<div><p>Signaling levels within sensory neurons must be tightly regulated to allow cells to integrate information from multiple signaling inputs and to respond to new stimuli. Herein we report a new role for the cGMP-dependent protein kinase EGL-4 in the negative regulation of G protein-coupled nociceptive chemosensory signaling. <i>C. elegans</i> lacking EGL-4 function are hypersensitive in their behavioral response to low concentrations of the bitter tastant quinine and exhibit an elevated calcium flux in the ASH sensory neurons in response to quinine. We provide the first direct evidence for cGMP/PKG function in ASH and propose that ODR-1, GCY-27, GCY-33 and GCY-34 act in a non-cell-autonomous manner to provide cGMP for EGL-4 function in ASH. Our data suggest that activated EGL-4 dampens quinine sensitivity via phosphorylation and activation of the regulator of G protein signaling (RGS) proteins RGS-2 and RGS-3, which in turn downregulate Gα signaling and behavioral sensitivity.</p></div

RGS proteins are targets of EGL-4.

<p>(A) Animals lacking each of the 8 neuronally expressed RGS proteins were tested for response to 1 mM quinine. <i>rgs-2(lof)</i> and <i>rgs-3(lof)</i> animals respond better than wild-type animals to dilute (1 mM) quinine (p<0.001). (B) RNAi knock-down of <i>rgs-2</i> or <i>rgs-3</i> in the quinine-detecting ASH sensory neurons of otherwise wild-type animals, using the <i>osm-10</i> promoter <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003619#pgen.1003619-Hart1" target="_blank">[3]</a>, resulted in behavioral hypersensitivity to dilute (1 mM) quinine, similar to <i>rgs-2(lof)</i> and <i>rgs-3(lof)</i> animals, respectively (p>0.05 for both transgenes when compared to the respective <i>rgs</i> loss-of-function animals). The <i>srb-6</i> promoter <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003619#pgen.1003619-Troemel2" target="_blank">[61]</a> was also used for ASH knock-down of <i>rgs-3</i>, and similarly resulted in hypersensitivity to 1 mM quinine (data not shown). (C) Wild-type animals overexpressing ectopic <i>rgs-2</i> or <i>rgs-3</i> cDNA displayed diminished response to 10 mM quinine (p<0.0001 when compared to wild-type animals). (D) <i>rgs-2(lof);egl-4(lof)</i> and <i>rgs-3(lof);egl-4(lof)</i> double mutant animals responded to dilute (1 mM) quinine similarly to <i>egl-4(lof)</i> animals (p>0.1 for each). (E) <i>egl-4(gof)</i> animals lacking either RGS-2 or RGS-3 function responded to 10 mM quinine similarly to the <i>rgs-2(lof)</i> and <i>rgs-3(lof)</i> animals, respectively (p>0.5) and (F) were hypersensitive to 1 mM quinine (p<0.001 when compared to wild-type animals). (G) <i>rgs-2(lof)</i> and <i>rgs-3(lof)</i> animals are hypersensitive to dilute (1 mM) quinine. ASH expression of wild-type RGS-2 or RGS-3, using the <i>osm-10</i> promoter <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003619#pgen.1003619-Hart1" target="_blank">[3]</a>, rescued quinine hypersensitivity in the respective loss-of-function animals. The predicted PKG phosphorylation target site in each was mutated (ΔP), making RGS-2(S126A) and RGS-3(S154A). <i>rgs-2(lof)</i> animals expressing RGS-2(ΔP) and <i>rgs-3(lof)</i> animals expressing RGS-3(ΔP) remained hypersensitive to dilute quinine (p>0.05 for each). The percentage of animals responding is shown. The combined data of ≥3 independent lines, n≥120 transgenic animals, is shown. Error bars represent the standard error of the mean (SEM). Alleles used: <i>egl-4(n479)</i>, <i>rgs-1(nr2017)</i>, <i>rgs-2(vs17)</i>, <i>rgs-3(vs19)</i>, <i>rgs-6(vs62)</i>, <i>rgs-10(ok1039)</i>, <i>rgs-10/11(vs109)</i>, <i>egl-10(md176)</i> and <i>eat-16(tm761)</i> loss-of-function and <i>egl-4(ad450)</i> gain-of-function. WT = the N2 wild-type strain. lof = loss-of-function. gof = gain-of-function.</p