Perinatal Lead (Pb) Exposure Results in Sex-Specific Effects on Food Intake, Fat, Weight, and Insulin Response across the Murine Life-Course

Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age

A new conceptual framework for revenge firesetting

Revenge has frequently been acknowledged to account for a relatively large proportion of motives in deliberate firesetting. However, very little is actually known about the aetiology of revenge firesetting. Theoretical approaches to revenge-seeking behaviour are discussed. A brief review of how revenge is accounted for in existing theoretical explanations of deliberate firesetting and the known characteristics of revenge firesetters are provided. On this basis, the authors suggest, as a motive, revenge firesetting has to date been misconceptualised. A new conceptual framework is thus proposed, paying particular attention to the contextual, affective, cognitive, volitional and behavioural factors which may influence and generate a single episode of revenge firesetting. Treatment implications and suggestions for future research are also provided

Syncytiotrophoblast Microvesicles Released from Pre-Eclampsia Placentae Exhibit Increased Tissue Factor Activity

Background: Pre-eclampsia is a complication of pregnancy associated with activation of coagulation. It is caused by the placenta, which sheds increased amounts of syncytiotrophoblast microvesicles (STBM) into the maternal circulation. We hypothesized that STBM could contribute to the haemostatic activation observed in pre-eclampsia. Methodology/Principal Findings: STBM were collected by perfusion of the maternal side of placentae from healthy pregnant women and women with pre-eclampsia at caesarean section. Calibrated automated thrombography was used to assess thrombin generation triggered by STBM-borne tissue factor in platelet poor plasma (PPP). No thrombin was detected in PPP alone but the addition of STBM initiated thrombin generation in 14/16 cases. Pre-eclampsia STBM significantly shortened the lag time (LagT, P = 0.01) and time to peak thrombin generation (TTP, P = 0.005) when compared to normal STBM. Blockade of tissue factor eliminated thrombin generation, while inhibition of tissue factor pathway inhibitor significantly shortened LagT (p = 0.01) and TTP (P,0.0001), with a concomitant increase in endogenous thrombin potential. Conclusions/Significance: STBM triggered thrombin generation in normal plasma in a tissue factor dependent manner, indicating that TF activity is expressed by STBM. This is more pronounced in STBM shed from pre-eclampsia placentae. As more STBM are shed in pre-eclampsia these observations give insight into the disordered haemostasis observed in thi

Enriching college students through study abroad: a case of Nepal Field Experience - Part 2

With a view of providing an unsurpassed opportunity to college students, who are mostly from Louisiana, in gaining a comprehensive understanding of Global Climate Change issues, we completed the first Nepal Field Experience Pilot Study Abroad from May 21-June 8, 2019. A total of fifteen students from the University of Louisiana at Lafayette, Louisiana, USA, and one graduate student from University of Arizona, Arizona, USA, participated in the program. Students examined and documented the effects of climate change impacts on agriculture, water resources, wildlife, local communities, forest resources, and other ecological and environmental settings of the country. They identified various climate change mitigation and adaptation measures that had been implemented and noted gaps between policy measures and ground realities. Research topics selected by the students included the following: climate change impacts on wildlife, water pollution, structural geology of Nepal, changing rainfall patterns and adaptation, climate change and agricultural production, geology of Kathmandu valley, air quality of Kathmandu valley, changing hydrology of glaciated landscape, climate change and geohazards, emerging diseases and pests on agricultural crops, climate change adaptation by local communities, green infrastructure and climate-smart technologies, climate change impact on drinking water sources, the roadside geology, and emerging diseases, parasites and zoonotics. Each student completed their individual research project, synthesized the results, and presented to local stakeholders in conference organized by a nonprofit nongovernmental organization, Asta-Ja Rsearch and Development Center (Asta-Ja RDC), Kathmandu, Nepal. Findings of the study reveal that Nepal is experiencing huge impacts of climate change in multiple fronts including atmospheric conditions and snowfall, temperature rise, occurrence of droughts and flooding, changes on monsoon pattern, emerging diseases and pests on crops and livestock, and declining drinking water sources. Environmental pollution, especially the air and water pollution and waste management, was very serious affecting public health, aesthetics, and even the tourism of the country. In order to reverse environmental degradation and enhance climate change adaptation, immediate implementation of effective, comprehensive, coordinated, and well-thought-out climate change adaptation and environmental initiatives are necessary. Nepal Field Experience was a lifetime learning experience for the students

Enriching college students through study abroad: a case of Nepal Field Experience - Part 1

With a view of providing an unsurpassed opportunity to college students, who are mostly from Louisiana, in gaining a comprehensive understanding of Global Climate Change issues, we completed the first Nepal Field Experience Pilot Study Abroad from May 21-June 8, 2019. A total of fifteen students from the University of Louisiana at Lafayette, Louisiana, USA, and one graduate student from University of Arizona, Arizona, USA, participated in the program. Students examined and documented the effects of climate change impacts on agriculture, water resources, wildlife, local communities, forest resources, and other ecological and environmental settings of the country. They identified various climate change mitigation and adaptation measures that had been implemented and noted gaps between policy measures and ground realities. Research topics selected by the students included the following: climate change impacts on wildlife, water pollution, structural geology of Nepal, changing rainfall patterns and adaptation, climate change and agricultural production, geology of Kathmandu valley, air quality of Kathmandu valley, changing hydrology of glaciated landscape, climate change and geohazards, emerging diseases and pests on agricultural crops, climate change adaptation by local communities, green infrastructure and climate-smart technologies, climate change impact on drinking water sources, the roadside geology, and emerging diseases, parasites and zoonotics. Each student completed their individual research project, synthesized the results, and presented to local stakeholders in conference organized by a nonprofit nongovernmental organization, Asta-Ja Rsearch and Development Center (Asta-Ja RDC), Kathmandu, Nepal. Findings of the study reveal that Nepal is experiencing huge impacts of climate change in multiple fronts including atmospheric conditions and snowfall, temperature rise, occurrence of droughts and flooding, changes on monsoon pattern, emerging diseases and pests on crops and livestock, and declining drinking water sources. Environmental pollution, especially the air and water pollution and waste management, was very serious affecting public health, aesthetics, and even the tourism of the country. In order to reverse environmental degradation and enhance climate change adaptation, immediate implementation of effective, comprehensive, coordinated, and well-thought-out climate change adaptation and environmental initiatives are necessary. Nepal Field Experience was a lifetime learning experience for the students

Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).</p> <p>Methods</p> <p>Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)</p> <p>Results</p> <p>HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.</p> <p>Conclusions</p> <p>The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.</p

The sperm factor: paternal impact beyond genes

The fact that sperm carry more than the paternal DNA has only been discovered just over a decade ago. With this discovery, the idea that the paternal condition may have direct implications for the fitness of the offspring had to be revisited. While this idea is still highly debated, empirical evidence for paternal effects is accumulating. Male condition not only affects male fertility but also offspring early development and performance later in life. Several factors have been identified as possible carriers of non-genetic information, but we still know little about their origin and function and even less about their causation. I consider four possible non-mutually exclusive adaptive and non-adaptive explanations for the existence of paternal effects in an evolutionary context. In addition, I provide a brief overview of the main non-genetic components found in sperm including DNA methylation, chromatin modifications, RNAs and proteins. I discuss their putative functions and present currently available examples for their role in transferring non-genetic information from the father to the offspring. Finally, I identify some of the most important open questions and present possible future research avenues