Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling.     

Mining of expressed sequence tag libraries of cacao for microsatellite markers using five computational tools

Expressed sequence tags (ESTs) provide researchers with a quick and inexpensive route for discovering new genes, data on gene expression and regulation, and also provide genic markers that help in constructing genome maps. Cacao is an important perennial crop of humid tropics. Cacao EST sequences, as available in the public domain, were downloaded and made into contigs. Microsatellites were located in these ESTs and contigs using five softwares (MISA, TRA, TROLL, SSRIT and SSR primer). MISA gave maximum coverage of SSRs in cacao ESTs and contigs, although TRA was able to detect higher order (>5-mer) repeats. The frequency of SSRs was one per 26.9 kb in the known set of ESTs. One-third of the repeats in EST-contigs were found to be trimeric. A few rare repeats like 21-mer repeat were also located. A/T repeats were most abundant among the mononucleotide repeats and the AG/GA/TC/CT type was the most frequent among dimerics. Flanking primers were designed using Primer3 program and verified experimentally for PCR amplification. The results of the study are made available freely online database (). Seven primer pairs amplified genomic DNA isolated from leaves were used to screen a representative set of 12 accessions of cacao.     

Germanium tetra(tertiary butoxide): Synthesis, structure and its utility as a precursor for the preparation of europium doped germanium oxide nanoparticles

Germanium tetra(tertiary butoxide), [Ge(O^tBu)₄], has been prepared by the reaction of GeCl₄ with KOBu^t in benzene. It is a monomeric crystalline solid having a distorted tetrahedral configuration, defined by the coordination of four OBu^t groups around germanium atom. The TG analysis showed that the compound is thermally stable and volatilizes at around 130 °C. Europium doped and un-doped germanium oxide nanoparticles were prepared based on the urea hydrolysis of Ge(O^tBu)₄/Eu(OOCCH₃)₃ in ethylene glycol medium at 150 °C followed by heating the resulting product at 750 °C. The nanoparticles were characterized by XRD, TEM and PL measurements. The europium doped nanoparticles, which were nearly monodispersed (∼30 nm), showed luminescence and the Eu³⁺ ions were occupying the surface of the GeO₂ nanoparticles.     

A Direct Brain-to-Brain Interface in Humans

We describe the first direct brain-to-brain interface in humans and present results from experiments involving six different subjects. Our non-invasive interface, demonstrated originally in August 2013, combines electroencephalography (EEG) for recording brain signals with transcranial magnetic stimulation (TMS) for delivering information to the brain. We illustrate our method using a visuomotor task in which two humans must cooperate through direct brain-to-brain communication to achieve a desired goal in a computer game. The brain-to-brain interface detects motor imagery in EEG signals recorded from one subject (the “sender”) and transmits this information over the internet to the motor cortex region of a second subject (the “receiver”). This allows the sender to cause a desired motor response in the receiver (a press on a touchpad) via TMS. We quantify the performance of the brain-to-brain interface in terms of the amount of information transmitted as well as the accuracies attained in (1) decoding the sender’s signals, (2) generating a motor response from the receiver upon stimulation, and (3) achieving the overall goal in the cooperative visuomotor task. Our results provide evidence for a rudimentary form of direct information transmission from one human brain to another using non-invasive means.     

Maternal hormonal interventions as a risk factor for Autism Spectrum Disorder: An epidemiological assessment from India

Globalization and women empowerment have led to stressful life among Indian women. This stress impairs women’s hormonal makeup and menstrual cycle, leading to infertility. National Family Health Survey-3 (NFHS-3) reports a decline in fertility status in India, indicating a rise in various infertility treatments involving hormonal interventions. No studies are available from India on the risk association link between maternal hormonal treatments and ASD. Hence, this study explores the association of maternal hormonal interventions with risk for ASD. Parents of 942 children (471 ASD and 471 controls) across 9 cities in India participated in the questionnaire-based study. The questionnaire was pilot tested and validated for its content and reliability as a psychometric instrument. Data collection was done at 70 centres through direct interaction with parents and with the help of trained staff. Statistical analysis of data was carried out using SAS 9.1.3. Out of the 471 ASD cases analysed, 58 mothers had undergone hormonal interventions (12.3%) while there were only 22 mothers among controls who underwent hormonal interventions (4.6%). According to logistic regression analysis maternal hormonal intervention (OR=2.24) was a significant risk factor for ASD.     

Cutaneous Injury-Related Structural Changes and Their Progression following Topical Nitrogen Mustard Exposure in Hairless and Haired Mice

To identify effective therapies against sulfur mustard (SM)-induced skin injuries, various animals have been used to assess the cutaneous pathology and related histopathological changes of SM injuries. However, these efforts to establish relevant skin injury endpoints for efficacy studies have been limited mainly due to the restricted assess of SM. Therefore, we employed the SM analog nitrogen mustard (NM), a primary vesicating and bifunctional alkylating agent, to establish relevant endpoints for efficient efficacy studies. Our published studies show that NM (3.2 mg) exposure for 12–120 h in both the hairless SKH-1 and haired C57BL/6 mice caused clinical sequelae of toxicity similar to SM exposure in humans. The NM-induced cutaneous pathology-related structural changes were further analyzed in this study and quantified morphometrically (as percent length or area of epidermis or dermis) of skin sections in mice showing these lesions. H&E stained skin sections of both hairless and haired mice showed that NM (12–120 h) exposure caused epidermal histopathological effects such as increased epidermal thickness, epidermal-dermal separation, necrotic/dead epidermis, epidermal denuding, scab formation, parakeratosis (24–120 h), hyperkeratosis (12–120 h), and acanthosis with hyperplasia (72–120 h). Similar NM exposure in both mice caused dermal changes including necrosis, edema, increase in inflammatory cells, and red blood cell extravasation. These NM-induced cutaneous histopathological features are comparable to the reported lesions from SM exposure in humans and animal models. This study advocates the usefulness of these histopathological parameters observed due to NM exposure in screening and optimization of rescue therapies against NM and SM skin injuries.     

Methylotrophic bacteria in sustainable agriculture

Excessive use of chemical fertilizers to increase production from available land has resulted in deterioration of soil quality. To prevent further soil deterioration, the use of methylotrophic bacteria that have the ability to colonize different habitats, including soil, sediment, water, and both epiphytes and endophytes as host plants, has been suggested for sustainable agriculture. Methylotrophic bacteria are known to play a significant role in the biogeochemical cycle in soil ecosystems, ultimately fortifying plants and sustaining agriculture. Methylotrophs also improve air quality by using volatile organic compounds such as dichloromethane, formaldehyde, methanol, and formic acid. Additionally, methylotrophs are involved in phosphorous, nitrogen, and carbon cycling and can help reduce global warming. In this review, different aspects of the interaction between methylotrophs and host plants are discussed, including the role of methylotrophs in phosphorus acquisition, nitrogen fixation, phytohormone production, iron chelation, and plant growth promotion, and co-inoculation of these bacteria as biofertilizers for viable agriculture practices.     

Nectar Robbing Positively Influences the Reproductive Success of Tecomella undulata (Bignoniaceae)

The net consequence of nectar robbing on reproductive success of plants is usually negative and the positive effect is rarely produced. We evaluated the influence of nectar robbing on the behaviour of pollinators and the reproductive success of Tecomella undulata (Bignoniaceae) in a natural population. Experimental pollinations showed that the trees were strictly self-incompatible. The three types of floral colour morphs of the tree viz. red, orange and yellow, lacked compatibility barriers. The pollinators (Pycnonotus cafer and Pycnonotus leucotis) and the robber (Nectarinia asiatica) showed equal preference for all the morphs, as they visited each morph with nearly equal frequency and flower-handling time. The sunbirds caused up to 60% nectar robbing, mostly (99%) by piercing through the corolla tube. Although nectar is replenished at regular intervals, insufficient amount of nectar compelled the pollinators to visit additional trees in bloom. Data of manual nectar robbing from the entire tree showed that the pollinators covered lower number of flowers per tree (5 flowers/tree) and more trees per bout (7 trees/bout) than the unrobbed ones (19 flowers/tree and 2 trees bout). The robbed trees set a significantly greater amount of fruits than the unrobbed trees. However, the number of seeds in a fruit did not differ significantly. The study shows that plant-pollinator-robber interaction may benefit the self-incompatible plant species under conditions that increases the visits of pollinators among the compatible conspecifics in a population.