Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer

Review of the articleMitochondria are the organelles responsible for producing the majority of a cell's ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend to bypass mechanisms for the maintenance of homoplasmy, potentially resulting in the transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by combinations of wild-type variants has been reported following cytoplasmic transfer (CT) in the human and following nuclear transfer (NT) in various animal species. Other techniques, such as germinal vesicle transfer and pronuclei transfer, have been proposed as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting embryos and offspring may contain mtDNA heteroplasmy, which itself could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is ensured before these techniques are used therapeutically

Regionalized Pathology Correlates with Augmentation of mtDNA Copy Numbers in a Patient with Myoclonic Epilepsy with Ragged-Red Fibers (MERRF-Syndrome)

Human patients with myoclonic epilepsy with ragged-red fibers (MERRF) suffer from regionalized pathology caused by a mutation in the mitochondrial DNA (m.8344A→G). In MERRF-syndrome brain and skeletal muscles are predominantly affected, despite mtDNA being present in any tissue. In the past such tissue-specificity could not be explained by varying mtDNA mutation loads. In search for a region-specific pathology in human individuals we determined the mtDNA/nDNA ratios along with the mutation loads in 43 different post mortem tissue samples of a 16-year-old female MERRF patient and in four previously healthy victims of motor vehicle accidents. In brain and muscle we further determined the quantity of mitochondrial proteins (COX subunits II and IV), transcription factors (NRF1 and TFAM), and VDAC1 (Porin) as a marker for the mitochondrial mass. In the patient the mutation loads varied merely between 89–100%. However, mtDNA copy numbers were increased 3–7 fold in predominantly affected brain areas (e.g. hippocampus, cortex and putamen) and in skeletal muscle. Similar increases were absent in unaffected tissues (e.g. heart, lung, kidney, liver, and gastrointestinal organs). Such mtDNA copy number increase was not paralleled by an augmentation of mitochondrial mass in some investigated tissues, predominantly in the most affected tissue regions of the brain. We thus conclude that “futile” stimulation of mtDNA replication per se or a secondary failure to increase the mitochondrial mass may contribute to the regionalized pathology seen in MERRF-syndrome

Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia

The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies.

Previous meta-analyses of intervention studies have come to different conclusions about effects of consumption of low-calorie sweeteners (LCS) on body weight. The present review included 60 articles reporting 88 parallel-groups and cross-over studies ≥1 week in duration that reported either body weight (BW), BMI and/or energy intake (EI) outcomes. Studies were analysed according to whether they compared (1) LCS with sugar, (2) LCS with water or nothing, or (3) LCS capsules with placebo capsules. Results showed an effect in favour of LCS vs sugar for BW (29 parallel-groups studies, 2267 participants: BW change, -1.06 kg, 95% CI -1.50 to -0.62, I2 = 51%), BMI and EI. Effect on BW change increased with 'dose' of sugar replaced by LCS, whereas there were no differences in study outcome as a function of duration of the intervention or participant blinding. Overall, results showed no difference in effects of LCS vs water/nothing for BW (11 parallel-groups studies, 1068 participants: BW change, 0.10 kg, 95% CI -0.87 to 1.07, I2 = 82%), BMI and EI; and inconsistent effects for LCS consumed in capsules (BW change: -0.28 kg, 95% CI -0.80 to 0.25, I2 = 0%; BMI change: 0.20 kg/m2, 95% CI 0.04 to 0.36, I2 = 0%). Occurrence of adverse events was not affected by the consumption of LCS. The studies available did not permit robust analysis of effects by LCS type. In summary, outcomes were not clearly affected when the treatments differed in sweetness, nor when LCS were consumed in capsules without tasting; however, when treatments differed in energy value (LCS vs sugar), there were consistent effects in favour of LCS. The evidence from human intervention studies supports the use of LCS in weight management, constrained primarily by the amount of added sugar that LCS can displace in the diet

On Chronology-Building for Central Thailand through an Attribute-Based Ceramic Seriation

This paper seeks to build a chronology for the prehistoric period and the early historic period of central Thailand. Sixteen ceramic assemblages from 14 prehistoric and early historic archaeological sites in the Pa Sak River valley (of central Thailand) were examined using an attribute-based seriation method. Body sherds were included in the study and the attributes selected for this study are those of surfacetreatment attributes. Correspondence analysis was used to seriate the 16 ceramic assemblages. Findings from this study suggest that surface-treatment attributes are temporally sensitive. The proposed chronology is thus based primarily on results of correspondence analysis of surface treatment. The final arrangement of the ceramic assemblages corresponds closely to broad archaeological periods proposed previously by Southeast Asian archaeologists. The results of correspondence analysis, however, provide a finer-scaled chronology for the study area. This research thus contributes to a better understanding of chronological development in the Central Plain of Thailand in general and in the Pa Sak River valley in particular. The research shows the significance and efficacy of attribute-based seriation and correspondence analysis as an exploratory multivariate method in the chronological placement of archaeological assemblages in Thailand and, by extension, in Southeast Asia. KEYWORDS: Southeast Asia, central Thailand, Pa Sak River valley, prehistoric and early historic periods, ceramic seriation, correspondence analysis

การลดค่าใช้จ่ายรวมที่เกี่ยวข้องกับของเสียประเภทรอยของแผ่นรองเครื่องเล่นซีดีStudy of Solidification Shrinkage Behavior in Cast Irons by Linear Displacement Method

งานวิจัยนี้มีวัตถุประสงค์เพื่อศึกษาพฤติกรรมการหดตัวและขยายตัวระหว่างการแข็งตัวของเหล็กหล่อเทา เหล็กหล่อแกรไฟต์ตัวหนอน และเหล็กหล่อเหนียว เพื่อบรรลุวัตถุประสงค์นี้จึงได้ประดิษฐ์อุปกรณ์พิเศษโดยอาศัยวิธีการวัดการเคลื่อนที่เชิงเส้น ซึ่งประกอบด้วยแบบหล่อทรายทรงกลมที่ผลิตด้วยกรรมวิธีแอดดิทีฟห่อหุ้มด้วยเปลือกเหล็กกล้าซึ่งมีเทอร์โมคัปเปิลและแท่งควอตซ์ (เชื่อมต่อกับอุปกรณ์วัดการเคลื่อนที่เชิงเส้น) เพื่อบันทึกอุณหภูมิและการเคลื่อนที่ได้ในเวลาเดียวกันเหล็กหล่อประเภทต่างๆ ที่มีคาร์บอนสมมูล 3.7, 4.0, 4.3 และ 4.6 ถูกผลิตขึ้นเพื่อการทดลอง จากการทดลองพบว่าพฤติกรรมการหดและขยายตัวของเหล็กหล่อทั้ง 3 ประเภท ต่างกันเล็กน้อย โดยการปริมาณการขยายตัวและเวลาการขยายตัวของแกรไฟต์เพิ่มขึ้นตามคาร์บอนสมมูลที่เพิ่มขึ้น มีอยู่ในช่วง 0.2–1.8 มิลลิเมตร และ 230–450 วินาที ตามลำดับ นอกจากนี้ยังพบการหดตัวเนื่องจากการเกิดออสเตนไนท์ในบางเงื่อนไขการทดลองที่คาร์บอนสมมูลต่ำกว่า 4.3 พฤติกรรมการแข็งตัวของเหล็กหล่อแต่ละประเภทไม่แตกต่างอย่างมีนัยสำคัญThis research aims to study the solidification behavior in Gray Iron (GI), Compacted Graphite Iron (CGI) and Ductile Iron (DI). In order to achieve this goal, the special equipment was devised by applying a linear displacement method. The equipment consisted of spherical additive-manufactured sand molds encased in steel jackets. The jackets were equipped with a thermocouple and quartz rod (connected to the LVDT) to record the temperature and the displacement simultaneously. Irons with various Carbon Equivalent (CE) 3.7, 4.0, 4.3 and 4.6 were produced for this experiment. It was found that the contraction and the expansion behaviors of three types of cast irons exhibited slight differences. The graphite expansion and graphite expansion time increased with increasing carbon equivalent ranged from 0.2–1.8 mm and 230–450 s respectively. In addition, the austenite shrinkage was observed for some conditions at CE lower than 4.3. No significant difference was seen between types of irons