Dropping out of an online mentoring program for girls in STEM: A longitudinal study on the dynamically changing risk for premature match closure

Premature closure of mentoring relationships decreases positive effects of mentoring or can even lead to negative effects for mentees. Past studies retrospectively investigated mechanisms of premature match closure. However, a deeper understanding of the dynamics that lead to premature match closure is still missing. In our study, we longitudinally examined the preprogram characteristics, program adherence, as well as program communication and networking behavior of girls (N = 901, M = 13.80 years) who took part in a 1-year online mentoring program in science, technology, engineering and mathematics (STEM), comparing girls who dropped out of the program prematurely (N = 598) with girls who were considered as non-dropouts (N = 303). We used survival analysis methods to simultaneously analyze time-independent characteristics and time-dependent dynamics of mentees' communication and networking behavior. Besides mentees' interest in STEM and compliance with program specifications, a frequent and steady communication with their mentors decreased the risk for premature match closure, especially, if it focused on STEM. Mentors' mentoring experience, mentees' program-wide networking and their networking with other mentees reduced the risk for premature match closure. Regarding the STEM focus of networking, we found competing influences, which need to be further explored in future research

Instillation of Six Different Ultrafine Carbon Particles Indicates a Surface Area Threshold Dose for Acute Lung Inflammation in Mice

Increased levels of particulate air pollution are associated with increased respiratory and cardiovascular mortality and morbidity. Some epidemiologic and toxicologic research suggests ultrafine particles (UFPs) (< 100 nm) to be more harmful per unit mass than larger particles. Our study was aimed at a quantitative comparison of acute adverse effects of different types of carbonaceous UFPs at a dose range that causes a moderate inflammatory response in lungs. We used six different particle types (primary particle size 10–50 nm, specific surface area 30–800 m(2)/g, and organic content 1–20%): PrintexG, Printex90, flame soot particles with different organic content (SootL, SootH), spark-generated ultrafine carbon particles (ufCP), and the reference diesel exhaust particles (DEP) SRM1650a. Mice were instilled with 5, 20, and 50 μg of each particle type, and bronchoalveolar lavage was analyzed 24 hr after instillation for inflammatory cells and the level of proinflammatory cytokines. At respective mass-doses, particle-caused detrimental effects ranked in the following order: ufCP > SootL ≥ SootH > Printex90 > PrintexG > DEP. Relating the inflammatory effects to the particle characteristics—organic content, primary particle size, or specific surface area—demonstrates the most obvious dose response for particle surface area. Our study suggests that the surface area measurement developed by Brunauer, Emmett, and Teller is a valuable reference unit for the assessment of causative health effects for carbonaceous UFPs. Additionally, we demonstrated the existence of a threshold for the particle surface area at an instilled dose of approximately 20 cm(2), below which no acute proinflammatory responses could be detected in mice

Loss of function mutation of the Slc38a3 glutamine transporter reveals its critical role for amino acid metabolism in the liver, brain, and kidney

Glutamine, the most abundant amino acid in mammals, is critical for cell and organ functions. Its metabolism depends on the ability of cells to take up or release glutamine by transporters located in the plasma membrane. Several solute carrier (SLC) families transport glutamine, but the SLC38 family has been thought to be mostly responsible for glutamine transport. We demonstrate that despite the large number of glutamine transporters, the loss of Snat3/Slc38a3 glutamine transporter has a major impact on the function of organs expressing it. Snat3 mutant mice were generated by N-ethyl-N-nitrosurea (ENU) mutagenesis and showed stunted growth, altered amino acid levels, hypoglycemia, and died around 20 days after birth. Hepatic concentrations of glutamine, glutamate, leucine, phenylalanine, and tryptophan were highly reduced paralleled by downregulation of the mTOR pathway possibly linking reduced amino acid availability to impaired growth and glucose homeostasis. Snat3-deficient mice had altered urea levels paralleled by dysregulation of the urea cycle, gluconeogenesis, and glutamine synthesis. Mice were ataxic with higher glutamine but reduced glutamate and gamma-aminobutyric acid (GABA) levels in brain consistent with a major role of Snat3 in the glutamine-glutamate cycle. Renal ammonium excretion was lower, and the expression of enzymes and amino acid transporters involved in ammoniagenesis were altered. Thus, SNAT3 is a glutamine transporter required for amino acid homeostasis and determines critical functions in various organs. Despite the large number of glutamine transporters, loss of Snat3 cannot be compensated, suggesting that this transporter is a major route of glutamine transport in the liver, brain, and kidney

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Claudin-12 is not required for blood-brain barrier tight junction function

Background The blood-brain barrier (BBB) ensures central nervous system (CNS) homeostasis by strictly controlling the passage of molecules and solutes from the bloodstream into the CNS. Complex and continuous tight junctions (TJs) between brain endothelial cells block uncontrolled paracellular diffusion of molecules across the BBB, with claudin-5 being its dominant TJs protein. However, claudin-5 deficient mice still display ultrastructurally normal TJs, suggesting the contribution of other claudins or tight-junction associated proteins in establishing BBB junctional complexes. Expression of claudin-12 at the BBB has been reported, however the exact function and subcellular localization of this atypical claudin remains unknown. Methods We created claudin-12-lacZ-knock-in C57BL/6J mice to explore expression of claudin-12 and its role in establishing BBB TJs function during health and neuroinflammation. We furthermore performed a broad standardized phenotypic check-up of the mouse mutant. Results Making use of the lacZ reporter allele, we found claudin-12 to be broadly expressed in numerous organs. In the CNS, expression of claudin-12 was detected in many cell types with very low expression in brain endothelium. Claudin-12(lacZ/lacZ) C57BL/6J mice lacking claudin-12 expression displayed an intact BBB and did not show any signs of BBB dysfunction or aggravated neuroinflammation in an animal model for multiple sclerosis. Determining the precise localization of claudin-12 at the BBB was prohibited by the fact that available anti-claudin-12 antibodies showed comparable detection and staining patterns in tissues from wild-type and claudin-12(lacZ/lacZ) C57BL/6J mice. Conclusions Our present study thus shows that claudin-12 is not essential in establishing or maintaining BBB TJs integrity. Claudin-12 is rather expressed in cells that typically lack TJs suggesting that claudin-12 plays a role other than forming classical TJs. At the same time, in depth phenotypic screening of clinically relevant organ functions of claudin-12(lacZ/lacZ) C57BL/6J mice suggested the involvement of claudin-12 in some neurological but, more prominently, in cardiovascular functions

The small SLC43 family: facilitator system l amino acid transporters and the orphan EEG1

The SLC43 family is composed of only three genes coding for the plasma membrane facilitator system l amino acid transporters LAT3 (SLC43A1; TC 2.A.1.44.1) and LAT4 (SLC43A2; TC 2.A.1.44.2), and the orphan protein EEG1 (SLC43A3; TC 2.A.1.44.3). Besides the known mechanism of transport of LAT3 and LAT4, their physiological roles still remain quite obscure. Morphants suggested a role of LAT3 in renal podocyte development in zebrafish. Expression in liver and skeletal muscle, and up-regulation by starvation suggest a role of LAT3 in the flux of branched-chain amino acids (BCAAs) from liver and skeletal muscle to the bloodstream. Finally, LAT3 is up-regulated in androgen-dependent cancers, suggesting a role in mTORC1 signaling in this type of tumors. In addition, LAT4 might contribute to the transfer of BCAAs from mother to fetus. Unfortunately, the EEG1 mouse model (EEG1(Y221∗)) described here has not yet offered a clue to the physiological role of this orphan protein

PMN cell numbers and IL-1β and MIP2 concentrations are plotted as a function of different characteristics of the instilled UFPs: () primary particle diameter (for an exemplary dose of 20 μg); () OC mass; and () particle surface area (BET)

<p><b>Copyright information:</b></p><p>Taken from "Instillation of Six Different Ultrafine Carbon Particles Indicates a Surface Area Threshold Dose for Acute Lung Inflammation in Mice"</p><p>Environmental Health Perspectives 2005;114(3):328-333.</p><p>Published online 22 Sep 2005</p><p>PMCID:PMC1392224.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p> Each symbol represents mean values of eight animals. A regression analysis revealed a strong logarithmic relation for the surface area ( = 0.65) and a weaker relation for the organic contribution ( = 0.38)

Threshold for inflammatory response for ufCP shown as the correlation between particle surface area and PMN cell numbers () or IL-1β () or MIP2 () concentrations

<p><b>Copyright information:</b></p><p>Taken from "Instillation of Six Different Ultrafine Carbon Particles Indicates a Surface Area Threshold Dose for Acute Lung Inflammation in Mice"</p><p>Environmental Health Perspectives 2005;114(3):328-333.</p><p>Published online 22 Sep 2005</p><p>PMCID:PMC1392224.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p> Two additional instilled doses of 0.5 and 2 μg, together with 5, 20, and 50 μg ufCP represent BET surface areas of 0.4, 16, 40, 161, and 404 cm, respectively. The dashed line indicates baseline levels of control animals; each circle represents the mean of eight animals