Prolactin Induces Tuberoinfundibular Dopaminergic Neurone Differentiation in Snell Dwarf Mice if Administered Beginning at 3 Days of Age

The hypothalamic tuberoinfundibular dopaminergic (TIDA) neurones secrete dopamine, which inhibits prolactin secretion. TIDA neurone numbers are deficient in Ames (df/df) and Snell (dw/dw) dwarf mice, which lack prolactin, growth hormone and thyroid-stimulating hormone. Prolactin therapy initiated before 21 days maintains normal-sized TIDA neurone numbers in df/df mice and, when initiated as early as 7 days, maintains the maximum TIDA neurone numbers observed in dw/dw development, which are decreased compared to those in normal mice. The present study investigated the effect of prolactin dose and species on TIDA neurone development. Snell dwarf and normal mice were treated with saline, 5 μg of ovine prolactin (oPRL), 50 μg of oPRL, or 50 μg of recombinant mouse prolactin (rmPRL) beginning at 3 days of age. Brains were analysed at 45 days using catecholamine histofluorescence, and immunohistochemistry for tyrosine hydroxylase or bromodeoxyuridine. Normal mice had greater (P ≤ 0.01) TIDA neurones than dw/dw, regardless of treatment. TIDA neurones in 50 μg oPRL-treated dw/dw mice were greater (P ≤ 0.05) than those in 5 μg oPRL- and rmPRL-treated dw/dw mice, which were greater (P ≤ 0.01) than those in saline-treated dw/dw mice. Fifty microgram oPRL-treated dw/dw mice also had greater (P < 0.01) TIDA neurone numbers than the maximum numbers observed in untreated dw/dw mice development. Among saline, 5 μg oPRL and 50 μg oPRL treatments, but not rmPRL, A14 neurone numbers were higher (P ≤ 0.01) in normal compared to in dw/dw mice. The mechanism of TIDA neurone recruitment was investigated using bromodeoxyuridine (BrdU) treatment at intervals after 21 days. Mice treated with rmPRL, but not oPRL, had increased BrdU incorporation in the periventricular area surrounding the third ventricle and median eminence and in the arcuate nucleus. The data obtained in the present study indicate that oPRL, but not rmPRL, when given at a high enough dose, induces TIDA neurone differentiation in dw/dw mice. This supports neurotrophic effects of prolactin on TIDA neurones in early postnatal development that extends beyond maintenance of the cell population

The IFN-γ-Inducible GTPase, Irga6, Protects Mice against Toxoplasma gondii but Not against Plasmodium berghei and Some Other Intracellular Pathogens

Clearance of infection with intracellular pathogens in mice involves interferon-regulated GTPases of the IRG protein family. Experiments with mice genetically deficient in members of this family such as Irgm1(LRG-47), Irgm3(IGTP), and Irgd(IRG-47) has revealed a critical role in microbial clearance, especially for Toxoplasma gondii. The in vivo role of another member of this family, Irga6 (IIGP, IIGP1) has been studied in less detail. We investigated the susceptibility of two independently generated mouse strains deficient in Irga6 to in vivo infection with T. gondii, Mycobacterium tuberculosis, Leishmania mexicana, L. major, Listeria monocytogenes, Anaplasma phagocytophilum and Plasmodium berghei. Compared with wild-type mice, mice deficient in Irga6 showed increased susceptibility to oral and intraperitoneal infection with T. gondii but not to infection with the other organisms. Surprisingly, infection of Irga6-deficient mice with the related apicomplexan parasite, P. berghei, did not result in increased replication in the liver stage and no Irga6 (or any other IRG protein) was detected at the parasitophorous vacuole membrane in IFN-γ-induced wild-type cells infected with P. berghei in vitro. Susceptibility to infection with T. gondii was associated with increased mortality and reduced time to death, increased numbers of inflammatory foci in the brains and elevated parasite loads in brains of infected Irga6-deficient mice. In vitro, Irga6-deficient macrophages and fibroblasts stimulated with IFN-γ were defective in controlling parasite replication. Taken together, our results implicate Irga6 in the control of infection with T. gondii and further highlight the importance of the IRG system for resistance to this pathogen

Integration of Wearable Sensors Into the Evaluation of Running Economy and Foot Mechanics in Elite Runners

Running economy, known as the steady-state oxygen consumption at a given submaximal intensity, has been proposed as one of the key factors differentiating East African runners from other running communities around the world. Kenyan runners have dominated middle- and long-distance running events and this phenomenon has been attributed, in part at least, to their exceptional running economy. Despite such speculation, there are no data on running mechanics during real-life situations such as during training or competition. The use of innovative wearable devices together with real-time analysis of data will represent a paradigm shift in the study of running biomechanics and could potentially help explain the outstanding performances of certain athletes. For example, the integration of foot worn inertial sensors into the training and racing of athletes will enable coaches and researchers to investigate foot mechanics (e.g., an accurate set of variables such as pitch and eversion angles, cadence, symmetry, contact and flight times or swing times) during real-life activities and facilitate feedback in real-time. The same technological approach also can be used to help the athlete, coach, sports physician, and sport scientist make better informed decisions in terms of performance and efficacy of interventions, treatments or injury prevention; a kind of "telesport" equivalent to "telemedicine." There also is the opportunity to use this real-time technology to advance broadcasting of sporting events with the transmission of real-time performance metrics and in doing so enhance the level of entertainment, interest, and engagement of enthusiasts in the broadcast and the sport. Such technological advances that are able to unobtrusively augment personal experience and interaction, represent an unprecedented opportunity to transform the world of sport for participants, spectators, and all relevant stakeholders

Ageing response of an Al-Mg-Mn-Sc-Zr alloy processed by laser metal deposition in thin-wall structures

The use of aluminium alloys containing Sc and Zr in additive manufacturing (AM) provides new solutions for lightweight design. Representative thin-wall structured parts were additively fabricated with a commercially available Al-4.55Mg-0.51Mn-0.65Sc-0.30Zr alloy in Laser Metal Deposition (LMD) process. A bi-directional and a uni-directional scan strategy were applied and laser power from 500 W to 600 W was used. Nanohardness tests were conducted on specimens aged at 300 °C for up to 19 h to observe the ageing responses. Fine-grained microstructures with few micro-sized precipitates containing Sc- and Zr were found in the last track of every specimen. The area formed by the track-overlapping was the opposite, but an apparent hardening was observed only after the ageing. AM-processes with local remelting are facing the challenge to exert the potential strengthening effect of aluminium alloys containing Sc. The mushy state must be suppressed to prevent the waste of the expensive rare elements