Common Bean Genetics, Breeding, and Genomics for Adaptation to Changing to New Agri-environmental Conditions

[EN] Common bean (Phaseolus vulgaris L.) has become, over the last 20 years, a competitive crop in national, regional, and international markets. This situation presents a dynamic environment for producers and researchers of this crop and requires a rethinking of current strategies against research and production needs, the opportunities and challenges of the future, and adaptation to changing agri-environmental conditions. Improvement of the common bean means possessing indepth knowledge of its genetic diversity, the genome and gene functions, to enable the analysis of pathways and networks in response to fluctuating environmental conditions. An important long-term challenge is the discovery of the gene(s) that control important production traits such as pest and disease resistance, abiotic stress tolerance,andbiologicalfixationofnitrogen.Thiswillneedtobeacooperativeworldwide effort that involves breeders, geneticists, and genomic and bioinformatics experts. Currently, newtechnologiesbuiltaroundtherecentlyreleasedcommonbeangenome sequence arenowbeingdeveloped,andvariousgenomicresourcesforcommonbean are available and include physical maps, bacterial artificial chromosome libraries, anchored physical and genetic maps, and expressed sequence tags. However, these approaches require precise phenotypic data. Complex interactions between the commonbeancropgenotype,environmentalfactorsincombinationwithplantpopulation dynamics and crop management greatly affect plant phenotypes in field experiments and are the key for the expansion of the productivity of this crop in traditional and nontraditional growing area

First molecular detection of Sarcocystis arctica (Apicomplexa: Sarcocystidae) infecting crab-eating raccoon (Procyon cancrivorus) in Brazil

Abstract The crab-eating raccoon (Procyon cancrivorus) is a wild carnivore with a broad geographic distribution, randing from Costa Rica to South America. This species remains understudied, particularly regarding Sarcocystis spp. infections. This study aimed to report the first molecular detection of Sarcocystis arctica in P. cancrivorus. The roadkill specimen, recovered from the highway of Pedro Osório, Rio Grande do Sul, Brazil, was subjected to necropsy. Tissues samples, bone marrow and blood were collected, and their genomic DNA was extracted. PCR amplification targeting 18S rRNA, COX1 and 28S genes, genetic sequencing and phylogenetic analysis confirmed the presence of S. arctica DNA in cardiac muscle samples. Molecular characterization showed 98.62-99.6% identity to sequences of this species deposited in GenBank. We report the first documentation of S. arctica infection in a P. cancrivorus heart sample. While species within the genus Procyon serve as definitive and intermediate hosts for other Sarcocystis species, it is uncertain whether P. cancrivorus acts as an aberrant host or plays a regular role in the protozoan life cycle, particularly in muscle tissue. Additionally, its impact on P. cancrivorus populations is still unknown, highlighting the need for further studies

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

New spinocerebellar ataxia subtype caused by <i>SAMD9L</i> mutation triggering mitochondrial dysregulation (SCA49)

Abstract Spinocerebellar ataxias consist of a highly heterogeneous group of inherited movement disorders clinically characterized by progressive cerebellar ataxia variably associated with additional distinctive clinical signs. The genetic heterogeneity is evidenced by the myriad of associated genes and underlying genetic defects identified. In this study, we describe a new spinocerebellar ataxia subtype in nine members of a Spanish five-generation family from Menorca with affected individuals variably presenting with ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals presented with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs, and a variable age of onset ranging from 12 to 60 years. Neurophysiological studies showed moderate axonal sensory polyneuropathy with altered sympathetic skin response predominantly in the lower limbs. We identified the c.1877C &amp;gt; T (p.Ser626Leu) pathogenic variant within the SAMD9L gene as the disease causative genetic defect with a significant log-odds score (Zmax = 3.43; θ = 0.00; P &amp;lt; 3.53 × 10−5). We demonstrate the mitochondrial location of human SAMD9L protein, and its decreased levels in patients’ fibroblasts in addition to mitochondrial perturbations. Furthermore, mutant SAMD9L in zebrafish impaired mobility and vestibular/sensory functions. This study describes a novel spinocerebellar ataxia subtype caused by SAMD9L mutation, SCA49, which triggers mitochondrial alterations pointing to a role of SAMD9L in neurological motor and sensory functions.</jats:p

Sleep disorders in parkinsonian and nonparkinsonian LRRK2 mutation carriers

OBJECTIVE: In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC). METHODS: A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD./nRESULTS: Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC. CONCLUSIONS: Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD.This manuscript received support through the grant number 061130/31 from "La Fundació la Marató de TV3" to Eduard Tolosa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers

Objective: In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC). Methods: A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD. Results: Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC. Conclusions: Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD

Patients with idiopathic Parkinson Disease associated with REM sleep behavior disorder.

<p><b>LEDD:</b> L-Dopa Equivalent daily dose; <b>M+AT</b>: polysomnographic montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle plus bilateral anterior tibialis phasic EMG activity in REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 46.4%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>Mentalis</b>: EMG activity quantification of "any" (tonic and phasic) type of EMG activity in the mentalis muscle during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 18.2%[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>MoCA</b>: Montreal Cognitive Assessment; <b>ND</b>: not done; <b>PIGD:</b> postural instability gait difficulty motor subtype; <b>SINBAR</b>: polysomnographyc montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorumsuperficialis muscles during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 32%[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>RBD</b>: REM sleep behaviour disorder; <b>RBDSQ:</b> REM sleep behavior disorder screening questionnaire; <b>TD</b>: tremor dominant motor subtype; <b>UPDRS-III</b>: Unified Parkinson Disease Rating Scale motor exam; <b>V-PSG</b>: video-polysomnography.</p><p>Patients with idiopathic Parkinson Disease associated with REM sleep behavior disorder.</p

Polysomnography and Multiple Sleep Latency Test data and comparisons between groups.

<p>Data are presented as mean, standard deviation, number and percentage.</p><p>*MSLT was performed in 17 out of 18 LRRK2-PD patients since one refused to undergo this test. Percentages on MSLT measures are therefore based on these 17 subjects.</p><p><b>AHI</b>: Apnea-hipopnea index; <b>LRRK2-PD</b>: LRRK2 Parkinson disease; <b>Mentalis</b>: polysomnographic montage quantifying "any" (phasic and tonic) type of EMG activity in the mentalis muscle during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 18%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>Mentalis plus AT</b>: polysomnographic montage quantifying "any" (phasic and tonic) type of EMG activity in the mentalis muscle plus phasic EMG activity in the right and left anterior tibialis during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 46.4%) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>MSLT</b>: Multiple Sleep Latency Test; <b>NMC</b>: non-manifesting carriers; <b>NMNC</b>: non-manifesting non-carriers; <b>NA</b>: Not applicable; <b>PLMS</b>: Periodic Leg Movements in Sleep; <b>PLMSI</b>: Periodic Leg Movements in Sleep Index; <b>RBD</b>: REM Sleep Behavior Disorder; <b>SINBAR</b>: polysomnographic montage quantifying "any" (phasic or tonic) type of EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorumsuperficialis muscles during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 32%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>SOREMPs</b>: Sleep Onset REM Sleep Periods.</p><p>Polysomnography and Multiple Sleep Latency Test data and comparisons between groups.</p

LRRK2-Parkinson Disease patients with associated REM sleep behavior disorder.

<p><b>LEDD</b>: L-Dopa Equivalent daily dose; <b>M+AT</b>: polysomnographic montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle plus bilateral anterior tibialis phasic EMG activity in REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 46.4%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>Mentalis</b>: EMG activity quantification of "any" (tonic and phasic) type of EMG activity in the mentalis muscle during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 18.2%.)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>MoCA</b>: Montreal Cognitive Assessment; <b>PIGD</b>: postural instability gait difficulty motor subtype; <b>SINBAR</b>: polysomnographyc montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorumsuperficialis muscles during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 32%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>RBD</b>: REM sleep behaviour disorder; <b>RBDSQ</b>: REM sleep behavior disorder screening questionnaire; <b>UPDRS-III</b>: Unified Parkinson Disease Rating Scale motor exam; <b>V-PSG:</b> video-polysomnography.</p><p>LRRK2-Parkinson Disease patients with associated REM sleep behavior disorder.</p

Subjects with restless legs syndrome.

<p><b>ESS</b>: Epworth Sleepiness Scale; <b>IRLSGRS</b>: International Restless-legs syndrome Study Group Scale; <b>LEDD</b>: L-Dopa Equivalent daily dose; <b>LRRK2-PD</b>: LRRK2 Parkinson disease subjects;<b>MSLT</b>: Multiple Sleep Latency Sleep Test; <b>NA</b>: Not applicable; <b>NMC</b>: Non-manifesting carriers; <b>NMNC</b>: Non-manifesting non-carriers; <b>PSQI</b>: Pittsburg Sleep Quality Index; <b>PDSS-2</b>: Parkinson Disease Sleep Scale 2; <b>PLMSI</b>: Periodic Leg Movements in Sleep Index; <b>RLS:</b> Restless Legs Syndrome.</p><p>Subjects with restless legs syndrome.</p