Molecular studies on a Dictyostelium homolog of the tafazzin gene, the cause of Barth syndrome in humans

Der eukaryotische Mikroorganismus Dictyostelium discoideum lebt als einzellige Amöbe solange ausreichende Nahrungsressourcen zur Verfügung stehen. Sobald Nahrungsmangel eintritt, entwickeln sich die Zellen von einem einzelligen zu einem mehrzelligen Zustand, der mit einem multizellulären Fruchtkörper abschließt. Dieser Prozess wird durch eine Reihe aufeinanderfolgender Signale organisiert, die eine differentielle Genexpression regulieren. Die Gene der Discoidin I Familie gehören zu den Ersten, die im Laufe des Wachstums-Differenzierungs-Übergangs (engl. GDT) aktiviert werden. Sie eignen sich daher vorzüglich als Marker für den Beginn der Entwicklung. Mit Hilfe einer REMI-Mutagenese und Discoidin I als molekularem Marker sind verschiedene Komponenten des Wachstums-Differenzierungs-Übergangs in unserer Arbeitsgruppe identifiziert worden (Zeng et al., 2000 A und B; Riemann und Nellen, persönliche Mitteilung). Mit demselben Ansatz wurde in der vorliegenden Arbeit eine REMI-Mutante identifiziert, die eine Fehl-Expression von Discoidin zeigte und einen axenischen Wachstumsdefekt bei 15 °C aufwies. Das Gen wurde als Homolog zum humanen Tafazzin-Gen identifiziert. Dieses Gen wurde zur Rekonstruktion des Phänotyps über homologe Rekombination erneut disruptiert, was wie erwartet zu dem zuerst beschriebenen Phänotyp führte. Folgerichtig ergab eine Überexpression des Gens in den Mutanten eine Komplementation des Phänotyps. Immunfluoreszenz-Experimente zeigten eine mitochondriale Lokalisation des Dictyostelium discoideum Taffazzin Proteins. Dass ein mitochondriales Protein in Zusammenhang mit dem Wachstums-Differenzierungs-Übergang steht, ist ein unerwarteter Befund, der aber als Hinweis darauf gewertet werden kann, dass Mitochondrien einen direkten Einfluss auf die entwicklungsspezifische Signaltransduktion ausüben. Die Taffazzin Disruptions-Mutante in Dictyostelium führte zu einem abnormalen Cardiolipin Metabolismus. Dieses Phospholipid ist ein charakteristischer Bestandteil der inneren Mitochondrienmembran und für die Funktion verschiedener Enzyme erforderlich. Unsere vorläufigen Analysen des Phospholipid-Gehalts zeigten Übereinstimmung mit Daten von Patienten mit Barth-Syndrom, einer humanen Erkrankung, bei der das Taffazzin-Gen Mutationen aufweist, und mit Hefe-Mutanten dieses Gens. Dies zeigt den Wert von Dictyostelium discoideum als einen weiteren Modelorganismus zur Untersuchung des Barth-Syndroms und zur Erprobung möglicher Therapieansätze.

Double burden malnutrition of preschool children and its association with brain development and milk consumption

Protecting the quality of children growth and development becomes a supreme qualification for the betterment of a nation. Double burden child malnutrition is emerging worldwide which might have a strong influence to the quality of child brain development and could not be paid-off on later life. Milk places a notable portion during the infancy and childhood. Thus, the deep insight on milk consumption pattern might explain the phenomenon of double burden child malnutrition correlated to the cognitive impairments. Objective: Current study is intended (1) to examine the current face of Indonesian double burden child malnutrition: a case study in Bogor, West Java, Indonesia, (2) to investigate the association of this phenomenon with child brain development, and (3) to examine the contribution of socioeconomic status and milk consumption on this phenomenon so that able to formulate some possible solutions to encounter this problem. Design: A cross-sectional study using a structured coded questionnaire was conducted among 387 children age 5-6 years old and their parents from 8 areas in Bogor, West-Java, Indonesia on November 2012 to December 2013, to record some socioeconomic status, anthropometric measurements, and history of breast feeding. Diet and probability of milk intake was assessed by two 24 h dietary recalls and food frequency questionnaire (FFQ). Usual daily milk intake was calculated using Multiple Source Method (MSM). Some brain development indicators (IQ, EQ, learning, and memory ability) using Projective Multi-phase Orientation method was also executed to learn the correlation between double burden child malnutrition and some brain development indicator. Results and conclusions: A small picture of child double burden malnutrition is shown in Bogor, West Java, Indonesia, where prevalence of Severe Acute Malnutrition (SAM) is 27.1%, Moderate Acute Malnutrition (MAM) is 24.9%, and overnutrition is 7.7%. This phenomenon proves to impair the child brain development. The malnourished children, both under- and over- nourished children have significantly (P-value<0.05) lower memory ability compared to the normal children (memory score, N; SAM = 45.2, 60; MAM = 48.5, 61; overweight = 48.4, 43; obesity = 47.9, 60; normal = 52.4, 163). The plausible reasons behind these evidences are the lack of nutrient intake during the sprout growth period on undernourished children or increasing adiposity on overnourished children might influence the growth of hippocampus area which responsible to the memory ability. Either undernutrition or overnutrition, the preventive action on this problem is preferable to avoid ongoing cognitive performance loss of the next generation. Some possible solutions for this phenomenon are promoting breast feeding initiation and exclusive breast feeding practices for infants, supporting the consumption of a normal portion of milk (250 to 500 ml per day) for children, and breaking the chain of poverty by socioeconomic improvement. And, the national food security becomes the fundamental point for the betterment of the next. In the global context, the causes of under- and over- nutrition have to be opposed through integrated and systemic approaches for a better quality of the next generation of human beings.

A pilot investigation of the relationship between climate variability and milk compounds under the bootstrap technique

This study analyzes the linear relationship between climate variables and milk components in Iran by applying bootstrapping to include and assess the uncertainty. The climate parameters, Temperature Humidity Index (THI) and Equivalent Temperature Index (ETI) are computed from the NASA-Modern Era Retrospective-Analysis for Research and Applications (NASA-MERRA) reanalysis (2002–2010). Milk data for fat, protein (measured on fresh matter bases), and milk yield are taken from 936,227 milk records for the same period, using cows fed by natural pasture from April to September. Confidence intervals for the regression model are calculated using the bootstrap technique. This method is applied to the original times series, generating statistically equivalent surrogate samples. As a result, despite the short time data and the related uncertainties, an interesting behavior of the relationships between milk compound and the climate parameters is visible. During spring only, a weak dependency of milk yield and climate variations is obvious, while fat and protein concentrations show reasonable correlations. In summer, milk yield shows a similar level of relationship with ETI, but not with temperature and THI. We suggest this methodology for studies in the field of the impacts of climate change and agriculture, also environment and food with short-term data.