Global analysis of yield benefits and risks from integrating trees with rice and implications for agroforestry research in Africa

While agroforestry is a well-established approach for agroecological intensification, rice is less often integrated with trees than other annual staple crops. The benefits and risks from rice agroforestry practices have not been systematically explored. Considering the need for strategies that may address low fertility and high degradation of arable soils and contribute to smallholder farm productivity, livelihoods and climate resilience, such exploration would both be timely and relevant. This study, therefore, reviews the published literature on integrating trees in rice production worldwide and provides perspectives for future research, with special attention to Africa, where the potential for sustainable productivity enhancement is deemed highest. Worldwide, six improved rice agroforestry practices are distinguished: hedgerow alley-cropping, short-term (0.5–4 years) improved fallows, pre-rice green manuring, biomass transfer, systematically arranged rice – tree intercropping and irregularly dispersed trees in fields. The rice agroforestry practices in the 87 publications reviewed were associated with 204 woody perennial species world-wide. Rice agroforestry practices provide a range of products and services to farmers but rice yield is the only quantitative performance indicator reported widely enough to enable meta-analysis. Frequently reported comparative or additional effects of fertilizer application, made it possible to include this aspect in the analyses. Across all types of agroforestry practices enumerated, the average effect of adding trees compared to a no-fertilizer and no-tree control is + 38%. The most beneficial practices in terms of enhancing rice yield were biomass transfer, pre-rice green manuring (100% of data points showing positive responses for both practices) and hedgerow alley-cropping (21% positive cases overall but 64% where fertilizer was not applied). Yield reductions occurred with fertilized intercropping compared to a fertilized mono-crop (in 95% of cases) and with the unfertilized short fallow practice (50% of data points showed yield reduction due to competition in the relay intercropping stage). Tree species that combined rice yield enhancements (alongside other products and services) with wide environmental adaptability across the African continent, include Sesbania rostrata, Aeschynomene afraspera, Acacia auriculiformis, Gliricidia sepium and Gmelia arborea. Yield benefits and risks from integrating trees with smallholder rice cropping depend on the type of agroforestry practice used and how each practice interacts with fertilizer application. Further research is needed to investigate the impact of different ways of integrating trees with rice cropping on wider environmental, social and economic sustainability aspects, that are driving increasing interest in rice agroforestry

Vulpia myuros, an increasing threat for agriculture

Vulpia myuros is an annual grass species of Mediterranean origin, which has achieved a global distribution. It is a fast-growing species, with high colonisation and competitive abilities. This species is considered an invasive weed in most countries where it has been introduced, with highly negative economic impact where it now dominates. It is increasingly found to be a problematic weed in winter cereals, especially in no-till and reduced tillage systems, across Europe, United States and Australia. Seeds of V. myuros have reduced germination potential when buried. However, where tillage interventions are reduced, ideal conditions for V. myuros are created. Minimum and no tillage practices are increasing worldwide, with a concomitant increase in the spread and abundance of V. myuros. Effectiveness of herbicides is mostly suboptimal, in particular for well-established populations forming dense swards, even though no herbicide resistance has yet been identified. An integrated management approach, increasing crop diversification combined with management adaptations, possibly including herbicides is suggested as an effective control strategy. Despite increasing research on V. myuros, more information is needed to optimise the management of this weed. Based on the species’ Mediterranean origins and adaptation to warm and dry environments, an increase of its global importance may be expected with climate changes. It is thus paramount to increase the awareness around this species, improve its identification in the field, and monitor its spread before it becomes a concern of similar magnitude to grass weeds like Alopecurus myosuroides or Lolium rigidum

Identification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBL

The EARS2 nuclear gene encodes mitochondrial glutamyl-tRNA synthetase, a member of the class I family of aminoacyl-tRNA synthetases (aaRSs) that plays a crucial role in mitochondrial protein biosynthesis by catalyzing the charging of glutamate to mitochondrial tRNA(Glu). Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The targeted sequencing of 150 nuclear genes encoding respiratory chain complex subunits and proteins implicated in the oxidative phosphorylation (OXPHOS) function was performed. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR), were measured. The enzymatic activities of Complexes I-V were analyzed spectrophotometrically. We describe a patient carrying two heterozygous EARS2 variants, c.376C>T (p.Gln126*) and c.670G>A (p.Gly224Ser), with infantile-onset disease and a severe clinical presentation. We demonstrate a clear defect in mitochondrial function in the patient’s fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants. Experimental validation using patient-derived fibroblasts allowed an accurate characterization of the disease-causing variants, and by comparing our patient’s clinical presentation with that of previously reported cases, new clinical and radiological features of LTBL were identified, expanding the clinical spectrum of this diseaseThis study was supported with a competitive PhD grant from a pre-Doctoral scholarship for research groups of the Health Research Institute of Santiago (IDIS)S

Mултисистемные поражение у детей: синдром NARP – митохондриальная болезнь (клинический случай)

Institute of Mother and Child, Chisinau, Republic of Moldova, Translational Metabolic Laboratory, Radboudumc, Nijmegen,Netherland, Institute of Psyhiology and Sancreatology, of Academy of Science, Chisinau, Republic of Moldova, State University of Medicine and Pharmacy, ”Nicolae Testemițanu”, Chisinau, Republic of MoldovaIntroducere. Maladiile mitocondriale fac parte din grupul tulburărilor neurodegenerative cauzate de dereglările ale generării energiei mitocondriale celulare. Sindromul NARP (neuropatie, ataxie și retinită pigmentară) este determinat de mutații punctiforme în gena MT-ATP6 din cadrul ADN-ului mitocondrial și este caracterizat prin variabilitatea manifestărilor clinice. Transmiterea mutației se realizează pe cale maternă, iar incidența este 1: 12.000 nașterii. Gravitatea manifestărilor clinice este asociată cu gradul de heteroplasmie a mutației ce determină patologia în cauză. Materiale și metode. Se raportează cazul unei fetițe, născută la termen, care s-a dezvoltat normal până la vârsta de 3 luni, însă ulterior a dezvoltat hipotonie, deficit ponderal, retard psiho-motor sever, dificultăți de alimentare, convulsii rezistente la terapie anticonvulsivantă, atrofie parțială a nervului optic și hepatomegalie. Investigațiile metabolice de bază, RMN-ul cerebral și analiza molecular-genetică au fost utilizate pentru diagnosticul patologiei mitocondriale. Rezultate. Luând în considerarea afectarea multisistemică și prezența manifestărilor clinice preponderent neurologice, pacientul a fost suspectat pentru o eroare înnăscută de metabolism. Inițial, considerând prezența hipotoniei progresive marcate ca simptom clinic cheie, s-a exclus Atrofia musculară spinală. În același timp a fost inițiat work-up-ul metabolic, dezvăluindu-se schimbări relevante pentru o maladie mitocondrială în sânge: hiperlactatacidemie [lactat 3.7-7.8 mmol/L, x 3 ori la rând, val. ref. 0.7-2.1 mmol/L], hiperalaninemie Ala [1038, val. ref. < 450 μmol/L], raportul Ala/Lys [11.8, abnormal dacă >3] și în urină: hiperaminoacidurie parțială. RMN cerebral (3,0T) – focare patologice la nivelul nucleilor bazali bilaterali. În urma sumării manifestărilor clinice și paraclinice s-au obținut 8 puncte ca scor specific pentru maladie mitocondrială definită (Criteriile Nijmegen). Nu a fost efectuată biopsia musculară, ca test confirmativ de diagnostic. Copilul a decedat la 9 luni de viață, iar diagnosticul molecular genetic la nivelul ADN-ului mitocondrial a fost efectuat postmortem în RadboudUMC (Nijmegen, Olanda), determinându-se mutația punctiformă m.8993T>G (Leu156Arg), cunoscută ca fiind determinantă în dezvoltarea sindromului NARP. Nu a fost posibilă aprecierea heteroplasmiei. Discuții. Sindromul NARP se caracterizează printr-o varietate de simptome și semne clinice cu preponderent de afectare neurologică. Diagnosticul acestei patologii deseori reprezintă o provocare pentru clinicieni determinată heterogenitate clinică care se suprapune cu alte maladii genetice. Debutul și evoluția simptomelor clinice depinde de gradul de heteroplasmie a mutației. Algoritmul de diagnosticul include inițierea work-upului metabolic, efectuarea RMN cerebral, biopsia musculară și determinarea mutației la nivel molecular genetic. Managmentul terapeutic rămâne a fi simptomatic pentru îmbunătățirea calității vieții pacientului. Concluzii. Debutul precoce, polimorfismul manifestărilor clinice, cum ar fi afectarea sistemului nervos central, slăbiciunea musculară, retardul psihomotor și convulsii în cazul unui copil ar trebui să determine clinicianul să ia în considerare sindromul NARP cu efectuarea investigațiilor suplimentare, cum ar fi măsurarea acidului lactic în sânge, efectuarea electromiografiei, rezonanței magnetice nucleare și testarea genetică.Introduction. Mitochondrial diseases are part of the group of neurodegenerative disorders caused by disruptions of cellular mitochondrial energy generation. NARP syndrome (Neurogenic weakness, ataxia, and retinitis pigmentosa) is caused by point mutations in the MT-ATP6 gene in mitochondrial DNA and is characterized by variability in clinical manifestations. The mutation is transmitted maternally, and the incidence is 1: 12,000 births. The severity of clinical manifestations is associated with the degree of heteroplasmia of the disease-causing mutation. Material and methods. We report on a case of a girl, born at term, who developed normally until the age of 3 months, but later developed hypotonia, weight deficit, severe psychomotor retardation, eating difficulties, seizures resistant to anticonvulsant therapy, partial atrophy of the optic nerve and hepatomegaly. Basic metabolic investigations, brain MRI and molecular-genetic analysis were used to diagnose mitochondrial pathology. Results. Considering the multisystemic impairment and the presence of predominantly neurological clinical manifestations, the patient was suspected of an innate metabolic error. Initially, considering the presence of marked progressive hypotonia as a key clinical symptom, spinal muscular atrophy was excluded. At the same time, the metabolic work-up was initiated, revealing relevant changes for a mitochondrial disease in the blood: hyperlactatacidemia [lactate 3.7-7.8 mmol/L, x 3 times in a row, ref. val. 0.7-2.1mmol / l], hyperalaninemia Ala [1038, ref. val. <450 μmol/L], Ala/ Lys ratio [11.8, abnormal if >3] and in urine: partial hyperaminoaciduria. Brain MRI (3.0T) – pathological foci in the bilateral basal nuclei. Following the summation of clinical and paraclinical manifestations, 8 points were obtained as a specific score for defined mitochondrial disease (Nijmegen Criteria). No muscle biopsy was performed as a confirmatory diagnostic test. The child died at 9 months of age, and the genetic molecular diagnosis of mitochondrial DNA was performed postmortem in RadboudUMC (Nijmegen, Netherlands), determining the point mutation m.8993T> G (Leu156Arg), known to be decisive in development of NARP syndrome. It was not possible to assess level of heteroplasmy. Discussions. NARP syndrome is characterized by a variety of symptoms and clinical signs, with predominantly neurological impairment. Diagnosis of this pathology is often a challenge for clinicians due to clinical heterogeneity that overlaps with other genetic diseases. The onset and development of clinical symptoms depends on the degree of heteroplasmic mutation. The diagnostic algorithm includes performing of metabolic work-up, brain MRI, muscle biopsy and genetic analysis. Therapeutic treatment is symptomatic and supportive of improving the patient’s quality of life. Conclusions. Early onset in the presence of complete health, the polymorphism of clinical manifestations, such as a central nervous system lesion, muscle weakness, impaired psychomotor development, and seizures in a child should prompt the clinician to consider NARP syndrome and conduct further investigations such as measurement of blood lactate, performing electromyography, magnetic resonance imaging, and genetic analysis.Введение. Митохондриальные заболевания относятся к группе нейродегенеративных заболеваний, вызванных нарушением выработки клеточной митохондриальной энергии. синдром NARP (Невропатия, атаксия, пигментная дегенерация сетчатки) вызывается точечными мутациями в гене MT-ATP6 в митохондриальной ДНК и характеризуется вариабельностью клинических проявлений. Мутаций передаются от матери, частота встречаемости составляет 1:12 000 рождении. Выраженность клинических проявлений связана со степенью гетероплазмии болезнетворной мутации.Материалы и методы. Мы сообщаем о клиническом случае доношенной девочке, которая нормально развивалась до 3 месяцев, но позже у нее развилась гипотония, дефицит веса, тяжелая психомоторная отсталость, трудности с питанием, судороги, устойчивые к противосудорожной терапии, частичная атрофия оптических нервов и гепатомегалия. Для диагностики митохондриальной патологии использовались базовые метаболические исследования, МРТ головного мозга и молекулярно-генетический анализ. Результаты. Учитывая мультисистемное нарушение и наличие преимущественно неврологических клинических проявлений, у пациента заподозрили врожденную метаболическую ошибку. Первоначально, учитывая наличие выраженной прогрессирующей гипотонии как ключевой клинический симптом, спинальная мышечная атрофия была исключена. В то же время, было начато исследование метаболизма, выявившее соответствующие изменения для митохондриального заболевания в крови: гиперлактатацидемия [лактат 3.7-7.8 ммоль/л, x 3 раза подряд, референсные значения 0.7-2.1 ммоль / л], гипераланинемия Ala [1038, референсные значения 3] и в моче: частичная гипераминоацидурия. МРТ головного мозга (3.0Т) – патологические очаги в двухсторонних базальных ядрах. После суммирования клинических и параклинических проявлений, было получено 8 баллов в качестве специфической оценки для определенного митохондриального заболевания (Неймегенские критерии). Биопсия мышц в качестве подтверждающего диагностического теста не проводилась. Ребенок умер в возрасте 9 месяцев, и генетическая молекулярная диагностика митохондриальной ДНК была проведена посмертно в RadboudUMC (Неймеген, Нидерланды), определив точечную мутацию m.8993T>G (Leu156Arg), которая, как известно, является решающей в развитии синдрома NARP. Оценка уровня гетероплазмии не удалось. Обсуждения. Синдром НАРП характеризуется множеством симптомов и клинических признаков с преимущественно неврологическими нарушениями. Диагностика этой патологии часто представляет собой проблему для клиницистов из-за клинической неоднородности, которая частично совпадает с другими генетическими заболеваниями. Возникновение и развитие клинических симптомов зависит от степени гетероплазмы мутации. Диагностический алгоритм включает в себя начало метаболических исследований, выполнение МРТ головного мозга, биопсию мышц и определение мутации на генетическом молекулярном уровне. Терапевтическое лечение остается симптомом улучшения качества жизни пациента. Заключение: Ранний дебют на фоне полного здоровья, полиморфизм клинических проявлений: поражение центральной нервной системы, мышечная слабость, нарушение психомоторного развития, судороги у ребенка, должны побуждать клинициста к рассмотрению синдрома NARP и проводить дальнейшие исследования, такие как измерение лактата в крови, выполнение электромиографии, магнитно-резонансной томографии и генетического анализа

Identification and Characterization of New Variants in FOXRED1 Gene Expands the Clinical Spectrum Associated with Mitochondrial Complex I Deficiency

Complex I (nicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase) is the largest complex of the mitochondrial oxidative phosphorylation system (OXPHOS) system. Forty-four subunits encoded in nuclear and mitochondrial genomes compose this multiprotein complex, its assembly being a highly complex process involving at least 15 additional nuclear encoded assembly factors. Complex I deficiency is a mitochondrial disorder usually associated with early-onset severe multisystem disorders characterized by highly variable clinical manifestations. Flavin adenine dinucleotide (FAD)-dependent oxidoreductase domain-containing protein 1 (FOXRED1) is a complex I assembly factor. To date, only five patients with mitochondrial complex I deficiency due to mutations in FOXRED1 have been characterized. Here, we describe a child with ataxia, epilepsy and psychomotor developmental delay carrying two heterozygous FOXRED1 variants, c.920G>A (p.Gly307Glu) and c.733+1G>A. We demonstrate the molecular mechanism supporting the pathogenicity of the FOXRED1 variants, showing a clear deficiency of complex I activity. The reduction in the steady-state level of complex I holoenzyme in patient fibroblasts, confirmed the pathogenicity of the variants and showed the molecular mechanism behind their pathogenicity. A comparison of the clinical presentation of the index case with the previously described cases allowed deepening our knowledge about the clinical variability associated with FOXRED1 defectsThis study was supported with a competitive Ph.D. grant by Pre-Doctoral scholarship, for research groups of the Health Research Institute of Santiago (IDIS)S

Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function

Contains fulltext : 191557.pdf (Publisher’s version ) (Open Access

A urinary biosignature for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS)

We used a comprehensive metabolomics approach to study the altered urinary metabolome of two mitochondrial myopathy, encephalopathy lactic acidosis and stroke like episodes (MELAS) cohorts carrying the m.3243A > G mutation. The first cohort were used in an exploratory phase, identifying 36 metabolites that were significantly perturbed by the disease. During the second phase, the 36 selected metabolites were able to separate a validation cohort of MELAS patients completely from their respective control group, suggesting usefulness of these 36 markers as a diagnostic set. Many of the 36 perturbed metabolites could be linked to an altered redox state, fatty acid catabolism and one-carbon metabolism. However, our evidence indicates that, of all the metabolic perturbations caused by MELAS, stalled fatty acid oxidation prevailed as being particularly disturbed. The strength of our study was the utilization of five different analytical platforms to generate the robust metabolomics data reported here. We show that urine may be a useful source for disease-specific metabolomics data, linking, amongst others, altered one-carbon metabolism to MELAS. The results reported here are important in our understanding of MELAS and might lead to better treatment options for the disease.Peer reviewe

Complete Issue 42(1)

Complete digitized issue (volume 42, issue 1, November 1959) of The Gavel of Delta Sigma Rho

NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2

Mutations in NDUFS4, which encodes an accessory subunit of mitochondrial oxidative phosphorylation (OXPHOS) complex I (CI), induce Leigh syndrome (LS). LS is a poorly understood pediatric disorder featuring brain-specific anomalies and early death. To study the LS pathomechanism, we here compared OXPHOS proteomes between various Ndufs4−/− mouse tissues. Ndufs4−/− animals displayed significantly lower CI subunit levels in brain/diaphragm relative to other tissues (liver/heart/kidney/skeletal muscle), whereas other OXPHOS subunit levels were not reduced. Absence of NDUFS4 induced near complete absence of the NDUFA12 accessory subunit, a 50% reduction in other CI subunit levels, and an increase in specific CI assembly factors. Among the latter, NDUFAF2 was most highly increased. Regarding NDUFS4, NDUFA12 and NDUFAF2, identical results were obtained in Ndufs4−/− mouse embryonic fibroblasts (MEFs) and NDUFS4-mutated LS patient cells. Ndufs4−/− MEFs contained active CI in situ but blue-native-PAGE highlighted that NDUFAF2 attached to an inactive CI subcomplex (CI-830) and inactive assemblies of higher MW. In NDUFA12-mutated LS patient cells, NDUFA12 absence did not reduce NDUFS4 levels but triggered NDUFAF2 association to active CI. BN-PAGE revealed no such association in LS patient fibroblasts with mutations in other CI subunit-encoding genes where NDUFAF2 was attached to CI-830 (NDUFS1, NDUFV1 mutation) or not detected (NDUFS7 mutation). Supported by enzymological and CI in silico structural analysis, we conclude that absence of NDUFS4 induces near complete absence of NDUFA12 but not vice versa, and that NDUFAF2 stabilizes active CI in Ndufs4−/− mice and LS patient cells, perhaps in concert with mitochondrial inner membrane lipids

Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis

Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome