From 'Farm to Fork': Exploring the Potential of Nutrient-Rich and Stress-Resilient Emergent Crops for Sustainable and Healthy Food in the Mediterranean Region in the Face of Climate Change Challenges.

In the dynamic landscape of agriculture and food science, incorporating emergent crops appears as a pioneering solution for diversifying agriculture, unlocking possibilities for sustainable cultivation and nutritional bolstering food security, and creating economic prospects amid evolving environmental and market conditions with positive impacts on human health. This review explores the potential of utilizing emergent crops in Mediterranean environments under current climate scenarios, emphasizing the manifold benefits of agricultural and food system diversification and assessing the impact of environmental factors on their quality and consumer health. Through a deep exploration of the resilience, nutritional value, and health impacts of neglected and underutilized species (NUS) such as quinoa, amaranth, chia, moringa, buckwheat, millet, teff, hemp, or desert truffles, their capacity to thrive in the changing Mediterranean climate is highlighted, offering novel opportunities for agriculture and functional food development. By analysing how promoting agricultural diversification can enhance food system adaptability to evolving environmental conditions, fostering sustainability and resilience, we discuss recent findings that underscore the main benefits and limitations of these crops from agricultural, food science, and health perspectives, all crucial for responsible and sustainable adoption. Thus, by using a sustainable and holistic approach, this revision analyses how the integration of NUS crops into Mediterranean agrifood systems can enhance agriculture resilience and food quality addressing environmental, nutritional, biomedical, economic, and cultural dimensions, thereby mitigating the risks associated with monoculture practices and bolstering local economies and livelihoods under new climate scenarios.

Research on Moringa (Moringa oleifera Lam.) in Africa.

While Moringa oleifera Lam. is gaining importance in Africa, especially sub-Saharan Africa, it is unclear whether research is following the quick pace of its development on the continent. Therefore, this article analyzes the landscape of research dealing with moringa in Africa. This systematic review draws upon 299 eligible articles identified through a search carried out on the Web of Science in April 2023. Research on M. oleifera is rather recent in Africa but interest is increasing among scholars. While the research field is multidisciplinary and cross-sectoral, the literature seems to focus on biological and environmental sciences. Moreover, research is performed mainly in South Africa, Nigeria, Egypt, and Ghana. The analysis suggests a significant potential contribution of moringa to food security and nutrition, climate change mitigation/adaptation, farming systems resilience, and livelihoods. Its versatility and diverse applications and uses make moringa particularly interesting for developing countries, such as African ones. However, this review also underscores some factors hindering its development. Therefore, there is a need to strengthen research on moringa to unlock its potential in Africa. Investments in research, innovation, and development can help address the many challenges that Africa faces and contribute to the transition towards sustainable and resilient food systems.

NUS1 Variants Cause Lennox-Gastaut Syndrome Related to Unfolded Protein Reaction Activation.

NUS1 encodes the Nogo-B receptor, a critical regulator for unfolded protein reaction (UPR) signaling. Although several loss-of-function variants of NUS1 have been identified in patients with developmental and epileptic encephalopathy (DEE), the role of the NUS1 variant in Lennox-Gastaut syndrome (LGS), a severe child-onset DEE, remains unknown. In this study, we identified two de novo variants of NUS1, a missense variant (c.868 C > T/p.R290C) and a splice site variant (c.792-2 A > G), in two unrelated LGS patients using trio-based whole-exome sequencing performed in a cohort of 165 LGS patients. Both variants were absent in the gnomAD population and showed a significantly higher observed number of variants than expected genome-wide. The R290C variant was predicted to damage NUS1 and decrease its protein stability. The c.792-2 A > G variant caused premature termination of the protein. Knockdown of NUS1 activated the UPR pathway, resulting in apoptosis of HEK293T cells. Supplementing cells with expression of wild-type NUS1, but not the mutant (R290C), rescued UPR activation and apoptosis in NUS1 knockdown cells. Compared to wild-type Drosophila, seizure-like behaviors and excitability in projection neurons were significantly increased in Tango14 (homolog of human NUS1) knockdown and Tango14R290C/+ knock-in Drosophila. Additionally, abnormal development and a small body size were observed in both mutants. Activated UPR signaling was also detected in both mutants. Thus, NUS1 is a causative gene for LGS with dominant inheritance. The pathogenicity of these variants is related to the UPR signaling activation, which may be a common pathogenic mechanism of DEE.

DHDDS and NUS1: A Converging Pathway and Common Phenotype.

BACKGROUND: Variants in dehydrodolichol diphosphate synthetase (DHDDS) and nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) cause a neurodevelopmental disorder, classically with prominent epilepsy. Recent reports suggest a complex movement disorder and an overlapping phenotype has been postulated due to their combined role in dolichol synthesis. CASES: We describe three patients with heterozygous variants in DHDDS and five with variants affecting NUS1. They bear a remarkably similar phenotype of a movement disorder dominated by multifocal myoclonus. Diagnostic clues include myoclonus exacerbated by action and facial involvement, and slowly progressive or stable, gait ataxia with disproportionately impaired tandem gait. Myoclonus is confirmed with neurophysiology, including EMG of facial muscles. LITERATURE REVIEW: Ninety-eight reports of heterozygous variants in DHDDS, NUS1 and chromosome 6q22.1 structural alterations spanning NUS1, confirm the convergent phenotype of hypotonia at birth, developmental delay, multifocal myoclonus, ataxia, dystonia and later parkinsonism with or without generalized epilepsy. Other features include periodic exacerbations, stereotypies, anxiety, and dysmorphisms. Although their gene products contribute to dolichol biosynthesis, a key step in N-glycosylation, transferrin isoform profiles are typically normal. Imaging is normal or non-specific. CONCLUSIONS: Recognition of their shared phenotype may expedite diagnosis through chromosomal microarray and by including DHDDS/NUS1 in movement disorder gene panels.

Perspectives on Retinal Dolichol Metabolism, and Visual Deficits in Dolichol Metabolism-Associated Inherited Disorders.

De novo synthesis of dolichol (Dol) and dolichyl phosphate (Dol-P) is essential for protein glycosylation. Herein, we provide a brief overview of Dol and Dol-P synthesis and the maintenance of their cellular content. Retinal Dol metabolism and the requirement of Dol-linked oligosaccharide synthesis in the neural retina also are discussed. There are recently discovered and an emerging class of rare congenital disorders that affect Dol metabolism, involving the genes DHDDS, NUS1, SRD5A3, and DOLK. Further understanding of these congenital disorders is evolving, based upon studies utilizing yeast and murine models, as well as clinical reports of these rare disorders. We summarize the known visual deficits associated with Dol metabolism disorders, and identify the need for generation and characterization of suitable animal models of these disorders to elucidate the underlying molecular and cellular mechanisms of the associated retinopathies.

Case report: splicing effect of a novel heterozygous variant of the NUS1 gene in a child with epilepsy.

NUS1 is responsible for encoding of the Nogo-B receptor (NgBR), which is a subunit of cis-prenyltransferase. Over 25 variants in NUS1 have been reported, and these variants have been found to be associated with various phenotypes, such as congenital disorders of glycosylation (CDG) and developmental and epileptic encephalopathy (DEE). We report on the case of a patient who presented with language and motor retardation, epilepsy, and electroencephalogram abnormalities. Upon conducting whole-exome sequencing, we discovered a novel pathogenic variant (chr6:118024873, NM_138459.5: c.791 + 6T>G) in NUS1, which was shown to cause Exon 4 to be skipped, resulting in a loss of 56 amino acids. Our findings strongly suggest that this novel variant of NUS1 is responsible for the development of neurological disorders, including epilepsy. It is believed that the truncation of Nogo-B receptor results in the loss of cis-prenyltransferase activity, which may be the underlying cause of the disease.

Novel NUS1 variant in a Chinese patient with progressive myoclonus epilepsy: a case report and systematic review.

BACKGROUND: Variants of the NUS1 gene have been associated with an extensive spectrum of phenotypes, including epilepsy, intellectual disability, cerebellar ataxia, Parkinson's disease, dystonia, and congenital disorder of glycosylation. It is rarely reported in progressive myoclonus epilepsy (PME). METHODS AND RESULTS: Herein, we report the case of PME caused by a novel de novo NUS1 missense variant (c.302T>A, p.Met101Lys). In addition, we reviewed the current literature of NUS1-associated PME. At present, five patients with NUS1 variants and PME have been reported in the literature. Due to limited cases reported, the relationship between NUS1 variants and PME is not well-established. CONCLUSIONS: Our case provides further evidence of the role of NUS1 variants in PME. These findings expand the clinical phenotypes of NUS1 variants, which should be included in the PME genetic screening panel.

nus-tool: A unified program for generating and analyzing sample schedules for nonuniformly sampled NMR experiments.

Increases in digital resolution achieved by high-field NMR require increases in spectral width. Additionally, the ability to resolve two overlapping peaks requires a sufficiently long acquisition time. These constraints combine, so that achieving high resolution spectra on high-field magnets requires long experiment times when employing uniform sampling and Fourier Transform processing. These limitations may be addressed by using nonuniform sampling (NUS), but the complexity of the parameter space across the variety of available NUS schemes greatly hinders the establishment of optimal approaches and best practices. We address these challenges with nus-tool, which is a software package for generating and analyzing NUS schedules. The nus-tool software internally implements random sampling and exponentially biased sampling. Through pre-configured plug-ins, it also provides access to quantile sampling and Poisson gap sampling. The software computes the relative sensitivity, mean evolution time, point spread function, and peak-to-sidelobe ratio; all of which can be determined for a candidate sample schedule prior to running an experiment to verify expected sensitivity, resolution, and artifact suppression. The nus-tool package is freely available on the NMRbox platform through an interactive GUI and via the command line, which is especially useful for scripted workflows that investigate the effectiveness of various NUS schemes.

Rhythmic cortical myoclonus in patients with 6Q22.1 deletion.

DNA deletions involving 6q22.1 region result in developmental encephalopathy (DE), often associated with movement disorders and epilepsy. The phenotype is attributed to the loss of the NUS1 gene included in the deleted region. Here we report three patients with 6q22.1 deletions of variable length all showing developmental delay, and rhythmic cortical myoclonus. Two patients had generalized seizures beginning in infancy. Myoclonic jerks had polygraphic features consistent with a cortical origin, also supported by cortico-muscular coherence analysis displaying a significant peak around 20 Hz contralateral to activated segment. Deletions in 6q22.1 region, similarly to NUS1 loss-of-function mutations, give rise to DE and cortical myoclonus via a haploinsufficiency mechanism. A phenotype of progressive myoclonic epilepsy (PME) may also occur.

Severity of behavioral addiction symptoms among young adults using non-prescribed sedatives/hypnotics.

Introduction: Young adulthood is considered a critical period in terms of non-medical use of sedatives/hypnotics (NMUSH) as well as different types of behavioral addictions (BAs). However, the relationship between these behaviors has received scarce attention among young adult samples. Therefore, the aim of the present study was to investigate the association between NMUSH and symptoms of distinct BAs among young adults. Materials and methods: Analyses were conducted based on the data of two large sample studies (including a representative sample) carried out with young adult samples. The following BAs were assessed: problematic internet use, problematic video gaming, problematic social media use, problem gambling, exercise addiction, eating disorders, compulsive buying behavior, problematic mobile phone use, work addiction, and hair pulling. Symptoms of distinct BAs were analyzed in three groups formed based on the NMUSH: non-users, lifetime users, and current users. Results: The symptoms of problematic internet use, problematic social media use, problem gambling, exercise addiction, eating disorders, compulsive buying behavior and work addiction were significantly more severe among lifetime and/or current non-medical sedative and hypnotic users, compared to the non-user participants. The symptoms of problematic mobile phone use were the most severe in the non-user group. Conclusions: The results suggest co-occurrence between NMUSH and distinct BAs among young adults. These findings draw attention to the need for preventive interventions for this high-risk population.

Chestnut Lily Beverage (CLB) Processing Using Ultrasound-Assisted Nisin: Microbiota Inactivation and Product Quality.

We evaluated the effects of ultrasound (US) and ultrasound combined with nisin (NUS) treatments on the properties of chestnut lily beverages (CLB) using conventional thermal pasteurisation (TP) as a control. After CLB samples were treated with US and NUS for 20, 40, or 60 min, the polyphenol oxidase activity (PPO), microbial inactivation effect, colour, pH value, total phenolic content, and antioxidant capacity of the CLB were observed. It was found that the inactivation rate of PPO in CLB after NUS treatment was higher than that in the US, indicating that NUS treatment aggravated PPO inactivation. Treatment time was important in the inactivation of microorganisms by US and NUS; NUS had a lethal synergistic lethal effect on microorganisms in CLB and when compared with US, NUS reduced changes in the CLB colour value. Notably, the total phenolic content and antioxidant capacity of the US- and NUS-treated CLB significantly increased relative to the TP group. These results that suggest NUS has a potential application value in the development of CLB because it reduces the risk of microorganism contamination and helps improve the quality of CLB. This study provides technical support and a theoretical basis for the improved production of CLB.

NUS1 and Epilepsy-myoclonus-ataxia Syndrome: An Under-recognized Entity?

Background: Variants of the NUS1 gene have recently been linked to a spectrum of phenotypes including epilepsy, cerebellar ataxia, cortical myoclonus and intellectual disability (ID), and primary congenital defects of glycosylation. Case Report: We report a case of myoclonus epilepsy, mild cerebellar ataxia, and ID due to a new de-novo NUS1 missense variant (c.868C>T, p.R290C), and review the current literature of NUS1-associated clinical phenotypes. Discussion: Pathogenic variants of NUS1 are found in a rapidly growing number of cases diagnosed with myoclonus epilepsy and/or myoclonus-ataxia syndrome. NUS1 should be included in the genetic screening of undiagnosed forms of myoclonus, myoclonus-ataxia, and progressive myoclonus epilepsies.

Decreased soluble Nogo-B in serum as a promising biomarker for Parkinson's disease.

Background: Recently, the neurite outgrowth inhibitor-B (Nogo-B) receptor has been reported as a novel candidate gene for Parkinson's disease (PD). Nogo-B receptors need to combine with soluble Nogo-B to exert their physiological function. However, little is known about the relationship between serum soluble Nogo-B and PD. Methods: Serum levels of sNogo-B and α-Synuclein (α-Syn) were measured in a cohort of 53 patients with PD and 49 healthy controls with the ELISA kit method. Results: Serum sNogo-B level is significantly lower in the PD group than that in healthy controls and is negatively correlated with UPDRS-III score (p = 0.049), H&Y stage (p = 0.0108) as well as serum α-Syn level (p = 0.0001). The area under the curve (AUC) of serum sNogo-B in differentiating patients with PD from controls was 0.801 while the AUC of serum α-Syn was 0.93. Combining serum sNogo-B and α-Syn in differentiating patients with PD from HC presented higher discriminatory potential (AUC = 0.9534). Conclusion: Decreased serum sNogo-B may be a potential biomarker for PD. Lower Nogo-B level reflects worse motor function and disease progression of PD. Serum sNogo-B is of added value to serum α-Syn panel in distinguishing PD from controls. Future studies are needed to confirm in larger samples and different populations.

High fidelity sampling schedules for NMR spectra of high dynamic range.

The ability to reconstruct non-uniformly sampled (NUS) NMR spectra has mostly been accepted. Still a concern is lingering regarding artifacts from sampling non-uniformly. As experienced, some sampling schedules yield better results than others. Finding a useful schedule is relatively trivial for a low dynamic range spectrum and a conservative sparsity, but not so when the dynamic range is large and/or when extreme sparsity is used. High dynamic range is typically found in NOESY and spectra of metabolites, where quantification of peak heights is desired at high fidelity. Extreme sparsity is desired when high throughput is a goal. In all cases, selecting a poor sampling schedule can create unnecessary artifacts. Effectively, it is important to select a sampling schedule that provides a signal-to-artifact apex ratio (SAAR) value in par or better than the signal-to-noise ratio (SNR) value. Notably, by signal-to-artifact apex ratio we consider reconstruction fidelity as the apex intensity likeness, i.e., as the true signal to the tallest artifact. We show that the quality of reconstruction depends on the particular sampling schedule. We evaluate the reconstruction quality in the frequency domain following a matched Lorentz-to-Gauss transform plus common apodization and Fourier Transform. As the Lorentz-to-Gauss transform improves resolution and reduces ridges we include this when defining the Signal-to-Artifact Apex Ratio (SAAR) metric. This metric measures the ratio of simulated reconstructed peak height to the tallest artifact of reconstruction in a spectrum without noise. Once a NUS schedule is found with an optimal SAAR it will be satisfactory for all spectra recorded with the same parameter set. Tables with good seed values are provided in the supplement.

Vascular healing after kissing balloon inflation: Nine-month 3D optical coherence tomography analysis in corelab.

Background: The jailing strut configuration with link-free and distal guidewire recrossing (LFD) at the side branch orifice (SBO) reduces incomplete stent apposition (ISA) after kissing balloon technique (KBT) in crossover stenting of coronary bifurcation lesions (CBLs). However, data regarding vascular healing after KBT are lacking. We investigated vascular healing 9 months after crossover stenting followed by KBT with optical coherence tomography (OCT) guidance in a prospective multicenter registry. Methods: Fifty-nine patients with CBLs (LFD, 35 patients; non-LFD, 24 patients) were studied. The jailing configuration of the SB and the wire-recrossing position, incidence of ISA and uncovered struts, and neointima unevenness score (NUS) in the main vessel (MV) after 9 months were determined by off-line 3D-OCT in the core laboratory. Results: The ISA rate was significantly higher at the SB ostium and distal MV after KBT in the non-LFD group, compared to the LFD group. After 9 months, incidence of ISA (18.3 ± 18.2 vs. 6.0 ± 8.7%, p < 0.01) and uncovered struts (8.7 ± 9.9 vs. 4.7 ± 7.3 %, p = 0.08) were higher at the SB ostium with higher SB restenosis in the non-LFD group. In distal MV, NUS was significantly higher (3.1 ± 1.1 vs. 2.5 ± 0.6, p < 0.05). In true-CBLs, an increase in uncovered struts and ISA rate was prominent in the proximal MV and opposite SB. No differences were observed in the 9-month clinical outcomes. Conclusion: Visualization of the wire recrossing point and the SB-jailing strut pattern by OCT plays an important role to optimize the KBT in CBL stenting, resulting in favorable mid-term vascular healing.

Improving keratoconus management with central cor neal regularization and corneal collagen cross-linking protocol treatment.

Purpose: To evaluate safety and efficacy of customized central corneal regularization (CCR), together with simultaneous accelerated corneal collagen cross-linking (A-CXL) - CCR-CXL protocol, to treat keratoconus-related corneal ectasia. Design: Retrospective, comparative observational case series. Methods: Patients that had undergone combined CCR-CXL protocol. Main inclusion criteria were keratoconus visual acuity deterioration and contact lens intolerance. All patients underwent complete ophthalmological evaluation, corrected distance visual acuity (CDVA) and Scheimpflug-corneal tomography. Central corneal regularization was performed by ablation using flying spot laser. Subsequently, the stroma was saturated with 0.17% riboflavin-5-phosphate added every 2 minutes, followed by A-CXL 9 mW/cm2 for 10 minutes. CDVA, medium keratometry value (Kmed), and total corneal morphological irregularity index (CMI) of patients were analyzed before surgery and after 1, 3 and 12 months. A P value of .05 or less was considered statistically significant. Results: 46 eyes of 39 keratoconus patients were treated. At 1 month, the mean CDVA (LogMar) increased from 0.19 ± 0.02 to 0.12 ± 0.02 (P < .05), and the difference remained stable at month 12. Kmax decrease was statistically significant from 57.02 ± 5.65 to 50.21 ± 4.48 (P < .05). CMI decreased significantly from 47.8 ± 2.84 to 30.1 ± 2.4 (P < .01). Conclusions: CCR-CXL protocol is safe and effective in arresting keratectasia progression and increasing corneal optic regularity in keratoconus. These findings showed a significant improvement in CDVA, keratometry values and corneal optical aberrations after being treated with the CCR-CXL protocol.

miR-184-5p inhibits cell proliferation, invasion and predicts prognosis of clear cell renal cell carcinoma by targeting NUS1 dehydrodolichyl diphosphate synthase subunit: Results from large-scale comprehensive identification and validation.

Clear cell renal cell carcinoma (ccRCC) has become a common malignant cancer with increasing incidence rate and high recurrence risk in genitourinary oncology around the world. Recently, miRNAs were identified to affect pathogenesis, development, molecular functions, and prognosis of ccRCC. In this study, microRNA-184-5p (miR-184-5p) was identified from three independent ccRCC cohorts and was determined as a significantly distinct prognostic biomarker. Relative miR-184-5p expression was found in A-498 and 786-O ccRCC cells compared with HK-2 cells. After ccRCC cells were transfected with miR-184-5p mimics or inhibitor, biological abilities of miR-184-5p in tumor cell proliferation, cycle, apoptosis and invasion were determined. Additionally, we confirmed the direct relationship between miR-184-5p and NUS1 dehydrodolichyl diphosphate synthase subunit (NUS1) by using the Luciferase reporter and rescue assays. These results indicated that the expression level of miR-184-5p in human ccRCC cells and tissues was reduced, and the up-regulation of miR-184-5p regulated A-498 and 786-O cell proliferation, invasion and apoptosis by directly targeting NUS1. These findings may provide new theoretical targets for treatment strategies and drug development of ccRCC.

Low-frequency and rare coding variants of NUS1 contribute to susceptibility and phenotype of Parkinson's disease.

NUS1 has been recently identified as a candidate gene for Parkinson's disease (PD). Few studies have examined the association of NUS1 variants with PD susceptibility and phenotypes. In the first cohort, whole-exome sequencing was performed to identify variants in NUS1 exon-coding and exon-intron regions in 1542 cases and 1625 controls. 13 variants were totally detected, of which 10 rare variants and 3 low-frequency variants. Burden analysis showed that rare NUS1 variants significantly enriched in PD (p=0.016). We also performed a meta-analysis based on previous and our studies to correlate NUS1 mutations with PD susceptibility. Integrating our previous cohort (3210 cases and 2807 controls) and the first cohort identified the significant association of rs539668656 with PD risk (odds ratio (OR) = 2.82, p = 0.016). The genotype-phenotype association analysis showed that patients carrying rare variants, or rs539668656 were significantly associated with earlier onset age, depression, emotional impairment and severe disease condition. Our results support the role of NUS1 rare variants and rs539668656 towards PD susceptibility and phenotype.

Use Patterns, Knowledge Diversity and Drivers for the Cultivation of the Miracle Plant [Synsepalum dulcificum (Schumach & Thonn.) Daniell] in Benin and Ghana.

Despite the growing interest in the miracle plant worldwide due to its numerous applications, the threats and the wild harvest of the species hamper its sustainable utilisation. Moreover, traditional knowledge so far documented on the species is limited to a narrow geographical coverage of its natural distribution range, which is West and Central Africa. This study analysed the use variation and knowledge acquisition pattern of the miracle plant among West African sociolinguistic groups and deciphered the drivers of populations' willingness and readiness to engage in cultivating the species. Semi-structured interviews were conducted with 510 respondents purposively selected from nine sociolinguistic groups in Benin and Ghana using the snowball sampling approach. Information was collected on respondents' socio-demographic profile, miracle plant ownership, plant parts used and preparation methods, knowledge of the species bioecology, perceived threats on the species, willingness to cultivate, maximum acreage to allocate to the species and maximum price to pay for a seedling. Descriptive statistics, generalized linear models, classification and regression tree models were used for data analysis. The miracle plant ownership mode depended on the age category. Sociolinguistic affiliation, level of schooling, migratory status and religion significantly affected the number of trees owned. We recorded 76 uses belonging to six use categories. The overall use-value of the miracle plant significantly varied according to the respondent sociolinguistic affiliation, main activity and religion. Men were the main source of knowledge and knowledge is mainly acquired along the family line. Knowledge related to food and social uses was mostly acquired from parents and people of the same generation, while magico-therapeutic and medicinal use-related knowledge were inherited from parents and grandparents. Sociolinguistic affiliation, awareness of taboos and market availability were the most important drivers of respondent willingness to cultivate the miracle plant. While the respondent's level of schooling and perception of plant growth rate determined the maximum acreage they were willing to allocate to the species in cultivation schemes, their main activity, sociolinguistic affiliation and knowledge of the species time to fruiting drove the maximum purchase price they were willing to offer for a seedling of the species. Our findings provide key information for the promotion of miracle plant cultivation in the study area.