YAP/Yorkie in the germline modulates the age-related decline of germline stem cells and niche cells

The properties and behaviour of stem cells rely heavily on signaling from the local microenvironment. At the apical end of Drosophila testis, self-renewal and differentiation of germline stem cells (GSCs) are tightly controlled by distinct somatic cells that comprise a specialised stem cell niche known as the hub. The hub maintains GSC homeostasis through adhesion and cell signaling. The Salvador/Warts/Hippo (SWH) pathway, which suppresses the transcriptional co-activator YAP/Yki via a kinase cascade, is a known regulator of stem cell proliferation and differentiation. Here, we show that increasing YAP/Yki expression in the germline, as well as reducing Warts levels, blocks the decrease of GSC numbers observed in aging flies, with only a small increase on their proliferation. An increased expression of YAP/Yki in the germline or a reduction in Warts levels also stymies an age-related reduction in hub cell number, suggesting a bilateral relationship between GSCs and the hub. Conversely, RNAi-based knockdown of YAP/Yki in the germline leads to a significant drop in hub cell number, further suggesting the existence of such a SC-to-niche relationship. All together, our data implicate the SWH pathway in Drosophila GSC maintenance and raise questions about its role in stem cell homeostasis in aging organisms

Immune consequences of exercise in hypoxia: A narrative review.

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type, dose (frequency/duration, intensity), and individual characteristics. Similarly, reduced availability of ambient oxygen (hypoxia) modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia. How combined exercise and hypoxia (e.g., high-altitude training) sculpts immune responses is not well understood, although such combinations are becoming increasingly popular. Therefore, in this paper, we summarize the impact on immune responses of exercise and of hypoxia, both independently and together, with a focus on specialized cells in the innate and adaptive immune system. We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia, then we discuss how they may be modulated by nutritional strategies. Mitochondrial, antioxidant, and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism, resilience, and overall immune functions by regulating the survival, differentiation, activation, and migration of immune cells. This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions. Appropriate acclimatization, training, and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state

Novel Characteristics of Valveless Pumping

This study investigates the occurrence of valveless pumping in a fluidfilled system consisting of two open tanks connected by an elastic tube. We show that directional flow can be achieved by introducing a periodic pinching applied at an asymmetrical location along the tube, and that the flow direction depends on the pumping frequency. We propose a relation between wave propagation velocity, tube length, and resonance frequencies associated with shifts in the pumping direction using numerical simulations. The eigenfrequencies of the system are estimated from the linearized system, and we show that these eigenfrequencies constitute the resonance frequencies and the horizontal slope frequencies of the system; 'horizontal slope frequency' being a new concept. A simple model is suggested, explaining the effect of the gravity driven part of the oscillation observed in response to the tank and tube diameter changes. Results are partly compared with experimental findings.Art. no. 22450

Technical aspects of boron neutron capture therapy at the BNL Medical Research Reactor

The Brookhaven Medical Research Reactor, BMRR, is a 3 MW heterogeneous, tank-type, light water cooled and moderated, graphite reflected reactor, which was designed for biomedical studies. Early BNL work in Boron Neutron Capture Therapy (BNCT) used a beam of thermal neutrons for experimental treatment of brain tumors. Research elsewhere and at BNL indicated that higher energy neutrons would be required to treat deep seated brain tumors. Epithermal neutrons would be thermalized as they penetrated the brain and peak thermal neutron flux densities would occur at the depth of brain tumors. One of the two BMRR thermal port shutters was modified in 1988 to include plates of aluminum and aluminum oxide to provide an epithermal port. Lithium carbonate in polyethylene was added in 1991 around the bismuth port to reduce the neutron flux density coming from outside the port. To enhance the epithermal neutron flux density, the two vertical thimbles A-3 (core edge) and E-3 (in core) were replaced with fuel elements. There are now four fuel elements of 190 grams each and 28 fuel elements of 140 grams each for a total of 4.68 kg of {sup 235}U in the core. The authors have proposed replacing the epithermal shutter with a fission converter plate shutter. It is estimated that the new shutter would increase the epithermal neutron flux density by a factor of seven and the epithermal/fast neutron ratio by a factor of two. The modifications made to the BMRR in the past few years permit BNCT for brain tumors without the need to reflect scalp and bone flaps. Radiation workers are monitored via a TLD badge and a self-reading dosimeter during each experiment. An early concern was raised about whether workers would be subject to a significant dose rate from working with patients who have been irradiated. The gamma ray doses for the representative key personnel involved in the care of the first 12 patients receiving BNCT are listed. These workers did not receive unusually high exposures

Stimulation of Na⁺/H⁺ Exchanger Isoform 1 Promotes Microglial Migration

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report

Women's leadership in the Asian Century: does expansion mean inclusion?

This paper draws on British Council commissioned research in response to concerns about women's absence from senior leadership positions in higher education in South Asia. The study sought existing knowledge from literature, policies, and available statistics and collected original interview data from 30 academics in Afghanistan, Bangladesh, India, Nepal, Pakistan, and Sri Lanka. A central finding was that gender is not a category of analysis in higher education policy, research or statistical data in the region. Our interview data suggest that leadership was frequently not an object of desire for women. Being associated with particular types of masculinities, leadership often carried a heavy affective load for those women who transgressed patriarchal socio-cultural norms and disrupted the symbolic order of women being led by men. Leadership was frequently perceived and experienced by women in terms of navigating a range of ugly feelings and toxicities that depleted aspirations, well-being and opportunities