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Widas Reservoir is situated in an area of 570 ha in the Pajaran Village, Madiun Regency, East Java Province, Indonesia, playing an essential role in fisheries, with the average fish catch per year of about 283 tons/year. This study explores the standing stock, growth parameters, mortality, and exploitation rates of several dominant fishes in Widas Reservoir. This study was carried out from February to November 2019. Fish stocks were estimated using acoustic tools, fish catch records, and sizes collected by local enumerators. Fish length frequency sampling was conducted on several dominant fish species, such as Oreochromis niloticus, Barbonymus gonionotus, and Osteochilus vittatus. Based on the length-frequency data, estimating fish population dynamics, the fish population dynamics (infinitive length (L∞) and growth coefficient (K)) estimation was run in a time series using the Fish Sock Analysis Tool, II (FISAT II) program package. Moreover, the estimation of natural mortality parameters, the fishing mortality parameter, and the exploitation rate was also performed. The approximated overall fish stock in the Widas Reservoir was about 79,848 kg, which lowered with the increase in water depth. Of particular concern, in the surface layer at a depth between 1–5 m, the fish stock reached 58,813 kg, while in the deeper zone (> 15 m), the value significantly lowered by about 98%, reaching 1,219 kg. These results indicate an overfishing in the Widas Reservoir. The value of the exploitation rate (E) of B. gonionotus was 0.748, O. niloticus 0.8, and O. vittatus 0.7, respectively, proving the overfishing states occurred in the study area. Therefore, regulations governing the number of catches and the use of fishing gear are crucial in Widas Reservoir, particularly the use of lift and gill nets with a mesh size of less than 2 cm.

Macrozoobenthos is a sedentary aquatic biota and is often used as a bioindicator for assessing water conditions. Therefore, this study aimed to investigate the species diversity of the macrozoobenthos and to analyze the heavy metal contamination in Faunus ater in the Rasian and Asahan estuaries in Aceh Province, Indonesia. The sampling was carried out in July 2022 on a squared transect of 1 m × 1 m for the collection of macrozoobenthos samples at random locations. The results showed that there were 17 macrozoobenthos species from both locations, of which 14 species were found in the Rasian River estuary and seven species in the Asahan River estuary. The diversity index of macrozoobenthos was in a moderate category. Terebralia sulcata had a higher density in the Asahan River, while F. ater had a higher density in the Rasian River. The results of the heavy metal analysis in the F. ater sample showed that this macrozoobenthos was contaminated by mercury, cadmium, and lead, of which the concentration of mercury exceeded the threshold limit, and they are, therefore, not safe for consumption.

Background: Early diagnosis of inherited metabolic diseases (IMDs) is important because treatment may lead to reduced mortality and improved prognosis. Due to their diversity, it is a challenge to diagnose IMDs in time, effecting an emerging need for a comprehensive test to acquire an overview of metabolite status. Untargeted metabolomics has proven its clinical potential in diagnosing IMDs, but is not yet widely used in genetic metabolic laboratories.Methods: We assessed the potential role of plasma untargeted metabolomics in a clinical diagnostic setting by using direct infusion high resolution mass spectrometry (DI-HRMS) in parallel with traditional targeted metabolite assays. We compared quantitative data and qualitative performance of targeted versus untargeted metabolomics in patients suspected of an IMD (n = 793 samples) referred to our laboratory for 1 year. To compare results of both approaches, the untargeted data was limited to polar metabolites that were analyzed in targeted plasma assays. These include amino acid, (acyl)carnitine and creatine metabolites and are suitable for diagnosing IMDs across many of the disease groups described in the international classification of inherited metabolic disorders (ICIMD).Results: For the majority of metabolites, the concentrations as measured in targeted assays correlated strongly with the semi quantitative Z-scores determined with DI-HRMS. For 64/793 patients, targeted assays showed an abnormal metabolite profile possibly indicative of an IMD. In 55 of these patients, similar aberrations were found with DI-HRMS. The remaining 9 patients showed only marginally increased or decreased metabolite concentrations that, in retrospect, were most likely to be clinically irrelevant. Illustrating its potential, DI-HRMS detected additional patients with aberrant metabolites that were indicative of an IMD not detected by targeted plasma analysis, such as purine and pyrimidine disorders and a carnitine synthesis disorder.Conclusion: This one-year pilot study showed that DI-HRMS untargeted metabolomics can be used as a first-tier approach replacing targeted assays of amino acid, acylcarnitine and creatine metabolites with ample opportunities to expand. Using DI-HRMS untargeted metabolomics as a first-tier will open up possibilities to look for new biomarkers.

Summary: The malate-aspartate shuttle (MAS) is a redox shuttle that transports reducing equivalents across the inner mitochondrial membrane while recycling cytosolic NADH to NAD+. We genetically disrupted each MAS component to generate a panel of MAS-deficient HEK293 cell lines in which we performed [U-13C]-glucose tracing. MAS-deficient cells have reduced serine biosynthesis, which strongly correlates with the lactate M+3/pyruvate M+3 ratio (reflective of the cytosolic NAD+/NADH ratio), consistent with the NAD+ dependency of phosphoglycerate dehydrogenase in the serine synthesis pathway. Among the MAS-deficient cells, those lacking malate dehydrogenase 1 (MDH1) show the most severe metabolic disruptions, whereas oxoglutarate-malate carrier (OGC)- and MDH2-deficient cells are less affected. Increasing the NAD+-regenerating capacity using pyruvate supplementation resolves most of the metabolic disturbances. Overall, we show that the MAS is important for de novo serine biosynthesis, implying that serine supplementation could be used as a therapeutic strategy for MAS defects and possibly other redox disorders.

Direct infusion–high-resolution mass spectrometry (DI-HRMS) allows for rapid profiling of complex mixtures of metabolites in blood, cerebrospinal fluid, tissue samples and cultured cells. Here, we present a DI-HRMS method suitable for the rapid determination of metabolic fluxes of isotopically labeled substrates in cultured cells and organoids. We adapted an automated annotation pipeline by selecting labeled adducts that best represent the majority of 13C and/or 15N-labeled glycolytic and tricarboxylic acid cycle intermediates as well as a number of their derivatives. Furthermore, valine, leucine and several of their degradation products were included. We show that DI-HRMS can determine anticipated and unanticipated alterations in metabolic fluxes along these pathways that result from the genetic alteration of single metabolic enzymes, including pyruvate dehydrogenase (PDHA1) and glutaminase (GLS). In addition, it can precisely pinpoint metabolic adaptations to the loss of methylmalonyl-CoA mutase in patient-derived liver organoids. Our results highlight the power of DI-HRMS in combination with stable isotopically labeled compounds as an efficient screening method for fluxomics.

Objectives: First, to compare the predictive performance of routine ultrasonographic estimated fetal weight (EFW) at 31 + 0 to 33 + 6 and 35 + 0 to 36 + 6 weeks' gestation for delivery of a small‐for‐gestational‐age (SGA) neonate. Second, to compare the predictive performance of EFW at 36 weeks' gestation for SGA vs fetal growth restriction (FGR) at birth. Third, to compare the predictive performance for delivery of a SGA neonate of EFW < 10th percentile vs a model combining maternal demographic characteristics and elements of medical history with EFW. Methods: This was a retrospective analysis of prospectively collected data in 21 676 women with a singleton pregnancy who had undergone routine ultrasound examination at 31 + 0 to 33 + 6 weeks' gestation and 107 875 women with a singleton pregnancy who had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks. Measurements of fetal head circumference, abdominal circumference and femur length were used to calculate EFW according to the Hadlock formula and this was expressed as a percentile according to the Fetal Medicine Foundation fetal and neonatal population weight charts. The same charts were used to diagnose SGA neonates with birth weight < 10th or < 3rd percentile. FGR was defined as birth weight < 10th percentile in addition to Doppler anomalies. For each gestational‐age window at screening, the screen‐positive rate and detection rate were calculated at different EFW cut‐offs between the 10th and 50th percentiles for predicting the delivery of a SGA neonate with birth weight < 10th or < 3rd percentile, either within 2 weeks or at any time after assessment. The areas under the receiver‐operating‐characteristics curves (AUC) of screening for a SGA neonate by EFW at 31 + 0 to 33 + 6 weeks and at 35 + 0 to 36 + 6 weeks were compared. Results: The predictive performance of routine ultrasonographic examination during the third trimester for delivery of a SGA neonate is higher if: first, the scan is carried out at 35 + 0 to 36 + 6 weeks' gestation rather than at 31 + 0 to 33 + 6 weeks; second, the outcome measure is birth weight < 3rd rather than < 10th percentile; third, the outcome measure is FGR rather than SGA; fourth, if delivery occurs within 2 weeks after assessment rather than at any time after assessment; and fifth, prediction is performed using a model that combines maternal demographic characteristics and elements of medical history with EFW rather than EFW < 10th percentile alone. At 35 + 0 to 36 + 6 weeks' gestation, detection of ≥ 85% of SGA neonates with birth weight < 10th percentile born at any time after assessment necessitates the use of EFW < 40th percentile. Screening at this percentile cut‐off predicted 95% and 98% of neonates with birth weight < 10th and < 3rd percentile, respectively, born within 2 weeks after assessment, and the respective values for neonates born at any time after assessment were 85% and 93%. Conclusion: Routine third‐trimester ultrasonographic screening for a SGA neonate performs best when the scan is carried out at 35 + 0 to 36 + 6 weeks' gestation, rather than at 31 + 0 to 33 + 6 weeks, and when EFW is combined with maternal risk factors to estimate the patient‐specific risk. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

NAD synthetase 1 (encoded by the gene NADSYN1) is a cytosolic enzyme that catalyzes the final step in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from tryptophan and nicotinic acid. NADSYN1 deficiency has recently been added to the spectrum of congenital NAD+ deficiency disorders. To gain insight into the metabolic consequences of NADSYN1 deficiency, the encoding gene was disrupted in A549 and HEK293T cells, and the metabolome was profiled in the presence of different NAD+ precursors, including tryptophan, nicotinamide and nicotinic acid. We demonstrate that when precursors of the NAD+ salvage pathway in the form of nicotinamide become limiting, NADSYN1 deficiency results in a decline in intracellular NAD+ levels even in the presence of other potential NAD+ sources such as tryptophan and nicotinic acid. As a consequence, alterations in 122 and 69 metabolites are observed in NADSYN1-deficient A549 and HEK293T cells compared to the wild-type cell line (FC > 2 and p < 0.05). We thus show that NADSYN1 deficiency results in a metabolic phenotype characterized by alterations in glycolysis, the TCA cycle, the pentose phosphate pathway, and the polyol pathway.

The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. The brain is dependent on vitamin B6 for its neurotransmitter balance. To obtain insight into the genetic determinants of vitamin B6 homeostasis, we conducted a genome-wide association study (GWAS) of the B6 vitamers pyridoxal (PL), PLP and the degradation product of vitamin B6, pyridoxic acid (PA). We collected a unique sample set of cerebrospinal fluid (CSF) and plasma from the same healthy human subjects of Dutch ancestry (n = 493) and included concentrations and ratios in and between these body fluids in our analysis. Based on a multivariate joint analysis of all B6 vitamers and their ratios, we identified a genome-wide significant association at a locus on chromosome 1 containing the ALPL (alkaline phosphatase) gene (minimal p = 7.89 × 10-10, rs1106357, minor allele frequency (MAF) = 0.46), previously associated with vitamin B6 levels in blood. Subjects homozygous for the minor allele showed a 1.4-times-higher ratio between PLP and PL in plasma, and even a 1.6-times-higher ratio between PLP and PL in CSF than subjects homozygous for the major allele. In addition, we observed a suggestive association with the CSF:plasma ratio of PLP on chromosome 15 (minimal p = 7.93 × 10-7, and MAF = 0.06 for rs28789220). Even though this finding is not reaching genome-wide significance, it highlights the potential of our experimental setup for studying transport and metabolism across the blood⁻CSF barrier. This GWAS of B6 vitamers identifies alkaline phosphatase as a key regulator in human vitamin B6 metabolism in CSF as well as plasma. Furthermore, our results demonstrate the potential of genetic studies of metabolites in plasma and CSF to elucidate biological aspects underlying metabolite generation, transport and degradation.

Abstract The 22q11.2 deletion syndrome (22q11.2DS) is characterized by a well-defined microdeletion and is associated with increased risk of neurodevelopmental phenotypes including autism spectrum disorders (ASD) and intellectual impairment. The typically deleted region in 22q11.2DS contains multiple genes with the potential of altering metabolism. Deficits in metabolic processes during early brain development may help explain the increased prevalence of neurodevelopmental phenotypes seen in 22q11.2DS. However, relatively little is known about the metabolic impact of the 22q11.2 deletion, while such insight may lead to increased understanding of the etiology. We performed untargeted metabolic analysis in a large sample of dried blood spots derived from 49 22q11.2DS patients and 87 controls, to identify a metabolic signature for 22q11.2DS. We also examined trait-specific metabolomic patterns within 22q11.2DS patients, focusing on intelligence (intelligence quotient, IQ) and ASD. We used the Boruta algorithm to select metabolites distinguishing patients from controls, patients with ASD from patients without, and patients with an IQ score in the lowest range from patients with an IQ score in the highest range. The relevance of the selected metabolites was visualized with principal component score plots, after which random forest analysis and logistic regression were used to measure predictive performance of the selected metabolites. Analysis yielded a distinct metabolic signature for 22q11.2DS as compared to controls, and trait-specific (IQ and ASD) metabolomic patterns within 22q11.2DS patients. The metabolic characteristics of 22q11.2DS provide insights in biological mechanisms underlying the neurodevelopmental phenotype and may ultimately aid in identifying novel therapeutic targets for patients with developmental disorders.

The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. The brain is dependent on vitamin B6 for its neurotransmitter balance. To obtain insight into the genetic determinants of vitamin B6 homeostasis, we conducted a genome-wide association study (GWAS) of the B6 vitamers pyridoxal (PL), PLP and the degradation product of vitamin B6, pyridoxic acid (PA). We collected a unique sample set of cerebrospinal fluid (CSF) and plasma from the same healthy human subjects of Dutch ancestry (n = 493) and included concentrations and ratios in and between these body fluids in our analysis. Based on a multivariate joint analysis of all B6 vitamers and their ratios, we identified a genome-wide significant association at a locus on chromosome 1 containing the ALPL (alkaline phosphatase) gene (minimal p = 7.89 × 10-10, rs1106357, minor allele frequency (MAF) = 0.46), previously associated with vitamin B6 levels in blood. Subjects homozygous for the minor allele showed a 1.4-times-higher ratio between PLP and PL in plasma, and even a 1.6-times-higher ratio between PLP and PL in CSF than subjects homozygous for the major allele. In addition, we observed a suggestive association with the CSF:plasma ratio of PLP on chromosome 15 (minimal p = 7.93 × 10-7, and MAF = 0.06 for rs28789220). Even though this finding is not reaching genome-wide significance, it highlights the potential of our experimental setup for studying transport and metabolism across the blood⁻CSF barrier. This GWAS of B6 vitamers identifies alkaline phosphatase as a key regulator in human vitamin B6 metabolism in CSF as well as plasma. Furthermore, our results demonstrate the potential of genetic studies of metabolites in plasma and CSF to elucidate biological aspects underlying metabolite generation, transport and degradation.

Comprehension is a critical part of the reading process, and yet learners continue to struggle with it and teachers continue to neglect it in their teaching. Many reasons exist for the lack of focus on reading comprehension instruction, but for the most part, teachers simply do not seem to view comprehension as part of the reading process, are not able to teach the concept, and are seemingly not taught to do so during their teacher training years. In addition to this, comprehension continues to be viewed as part of "language teaching", and is therefore viewed as the so-called "language teacher's" domain. In support of effective comprehension instruction in the unique, multilingual South African education environment, this article proposes a framework for reading strategy instruction, aimed specifically at teachers. The framework was developed from a research study, and refined through subsequent application in a university course as well as a further study. The framework acknowledges that reading is a multifaceted and complex process, and accordingly, provides sufficient structure for teachers. It further addresses the issue of comprehension instruction through the use of selected reading strategies, designed to be applied by all teachers in all subjects in a flexible and easy manner.

Widas Reservoir is a multifunctional resource with potential for fisheries, but its water quality can be significantly affected by various activities. This research aims to determine the status of trophic levels and water quality, which is crucial for water resource management and conservation. The study involved a comprehensive field survey with sampling at various points, considering the inlets, outlets, and conservation zones. The research found that the average water depth was 10.9 meters, transparency was 511 centimeters, CO2 concentration ranged from 0.0 to 17.6 mg/L, DO ranged from 0.1 to 8.2 mg/L, and temperature ranged from 25 to 31.1°C. In addition, temperature and DO decrease with depth, in contrast to CO2, which tends to increase with depth. The average conductivity was 150.3 µmhos/cm, total alkalinity was 103.1 mg/L, turbidity was 63 NTU, pH ranged from 6 to 8, and phosphate (PO4) concentration averaged 28.74 µg/L. TP average was 33.39 µg/L, and Chlorophyll-a averaged 21.75 μg/L. The Trophic Status Index (TSI) showed a high fertility (eutrophic) level with an average index value of 63.8. The potential for fish production was high at 626.6 kg/ha/year. [ABSTRACT FROM AUTHOR]

I report on teacher change in the context of a reading strategy instruction intervention. Reading Strategy Instruction (RSI) was implemented by three teachers, new to the concept, over a period of 15 weeks. Observations of these teachers showed that a multitude of factors affect the uptake of RSI as part of everyday teaching practice, and that teachers seem to move through distinct phases in their uptake of RSI. The article focuses on teachers' reaction to RSI and highlights a number of issues that are important to the implementation of RSI, not the least of which is that a clear need exists for changes to in-service teacher training and support and pre-service teacher training. In an effort to address these training issues the article contains specific recommendations for pre-service teacher training in particular.

Direct infusion–high-resolution mass spectrometry (DI-HRMS) allows for rapid profiling of complex mixtures of metabolites in blood, cerebrospinal fluid, tissue samples and cultured cells. Here, we present a DI-HRMS method suitable for the rapid determination of metabolic fluxes of isotopically labeled substrates in cultured cells and organoids. We adapted an automated annotation pipeline by selecting labeled adducts that best represent the majority of 13C and/or 15N-labeled glycolytic and tricarboxylic acid cycle intermediates as well as a number of their derivatives. Furthermore, valine, leucine and several of their degradation products were included. We show that DI-HRMS can determine anticipated and unanticipated alterations in metabolic fluxes along these pathways that result from the genetic alteration of single metabolic enzymes, including pyruvate dehydrogenase (PDHA1) and glutaminase (GLS). In addition, it can precisely pinpoint metabolic adaptations to the loss of methylmalonyl-CoA mutase in patient-derived liver organoids. Our results highlight the power of DI-HRMS in combination with stable isotopically labeled compounds as an efficient screening method for fluxomics. [ABSTRACT FROM AUTHOR]

D-lactic acidosis typically occurs in the context of short bowel syndrome; excess D-lactate is produced by intestinal bacteria. Here, the authors identify two point mutations in the human lactate dehydrogenase D (LDHD) gene that cause enzymatic loss of function and are associated with elevated plasma D-lactate.

The diagnostic evaluation and clinical characterization of rare hereditary anemia (RHA) is to date still challenging. In particular, there is little knowledge of the broad metabolic impact of many of the molecular defects underlying RHA. In this study we explored the potential of untargeted metabolomics to diagnose a relatively common type of RHA: pyruvate kinase deficiency (PKD). In total, 1,903 unique metabolite features were identified in dried blood spot samples from 16 PKD patients and 32 healthy controls. A metabolic fingerprint was identified using a machine learning algorithm, and subsequently a binary classification model was designed. The model showed high performance characteristics (AUC 0.990, 95% CI: 0.981-0.999) and an accurate class assignment was achieved for all newly added control (n=13) and patient samples, (n=6) with the exception of one patient (accuracy 94%). Important metabolites in the metabolic fingerprint included glycolytic intermediates, polyamines and several acyl carnitines. In general, the application of untargeted metabolomics in dried blood spots is a novel functional tool that holds promise for the diagnostic stratification and studies on the disease pathophysiology in RHA.

Introduction: Hartnup disorder is caused by a deficiency of the sodium dependent B0 AT1 neutral amino acid transporter in the proximal kidney tubules and jejunum. Biochemically, Hartnup disorder is diagnosed via amino acid excretion patterns. However, these patterns can closely resemble amino acid excretion patterns of generalized aminoaciduria, which may induce a risk for misdiagnosis and preclusion from treatment. Here we explore whether calculating a diagnostic ratio could facilitate correct discrimination of Hartnup disorder from other aminoacidurias. Methods: 27 amino acid excretion patterns from 11 patients with genetically confirmed Hartnup disorder were compared to 68 samples of 16 patients with other aminoacidurias. Amino acid fold changes were calculated by dividing the quantified excretion values over the upper limit of the age-adjusted reference value. Results: Increased excretion of amino acids is not restricted to amino acids classically related to Hartnup disorder (“Hartnup amino acids”, HAA), but also includes many other amino acids, not classically related to Hartnup disorder (“other amino acids”, OAA). The fold change ratio of HAA over OAA was 6.1 (range: 2.4–9.6) in the Hartnup cohort, versus 0.2 (range: 0.0–1.6) in the aminoaciduria cohort (p