Workshops without Walls: Broadening Access to Science around the World

The National Aeronautics and Space Administration (NASA) Astrobiology Institute (NAI) conducted two “Workshops Without Walls” during 2010 that enabled global scientific exchange—with no travel required. The second of these was on the topic “Molecular Paleontology and Resurrection: Rewinding the Tape of Life.” Scientists from diverse disciplines and locations around the world were joined through an integrated suite of collaborative technologies to exchange information on the latest developments in this area of origin of life research. Through social media outlets and popular science blogs, participation in the workshop was broadened to include educators, science writers, and members of the general public. In total, over 560 people from 31 US states and 30 other nations were registered. Among the scientific disciplines represented were geochemistry, biochemistry, molecular biology and evolution, and microbial ecology. We present this workshop as a case study in how interdisciplinary collaborative research may be fostered, with substantial public engagement, without sustaining the deleterious environmental and economic impacts of travel

Fgf15 Neurons of the Dorsomedial Hypothalamus Control Glucagon Secretion and Hepatic Gluconeogenesis.

The counterregulatory response to hypoglycemia is an essential survival function. It is controlled by an integrated network of glucose-responsive neurons, which trigger endogenous glucose production to restore normoglycemia. The complexity of this glucoregulatory network is, however, only partly characterized. In a genetic screen of a panel of recombinant inbred mice we previously identified Fgf15, expressed in neurons of the dorsomedial hypothalamus (DMH), as a negative regulator of glucagon secretion. Here, we report on the generation of Fgf15 <sup>CretdTomato</sup> mice and their use to further characterize these neurons. We show that they were glutamatergic and comprised glucose-inhibited and glucose-excited neurons. When activated by chemogenetics, Fgf15 neurons prevented the increase in vagal nerve firing and the secretion of glucagon normally triggered by insulin-induced hypoglycemia. On the other hand, they increased the activity of the sympathetic nerve in the basal state and prevented its silencing by glucose overload. Higher sympathetic tone increased hepatic Creb1 phosphorylation, Pck1 mRNA expression, and hepatic glucose production leading to glucose intolerance. Thus, Fgf15 neurons of the DMH participate in the counterregulatory response to hypoglycemia by a direct adrenergic stimulation of hepatic glucose production while suppressing vagally induced glucagon secretion. This study provides new insights into the complex neuronal network that prevents the development of hypoglycemia

A minimally invasive technique for short spiral implant insertion with contextual crestal sinus lifting in the atrophic maxilla: A preliminary report

The most recently reported techniques for the rehabilitation of the atrophic posterior maxilla are increasingly less invasive, as they are generally oriented to avoid sinus floor elevation with lateral access. The authors describe a mini-invasive surgical technique for short spiral implant insertion for the prosthetic rehabilitation of the atrophic posterior maxilla, which could be considered a combination of several previously described techniques based on the under-preparation of the implant site to improve fixture primary stability and crestal approach to the sinus floor elevation without heterologous bone graft. Eighty short spiral implants were inserted in the molar area of the maxilla in patients with 4.5–6 mm of alveolar bone, measured on pre-operative computed tomography. The surgical technique involved careful drilling for the preparation of implant sites at differentiated depths, allowing bone dislocation in the apical direction, traumatic crestal sinus membrane elevation, and insertion of an implant (with spiral morphology) longer than pre-operative measurements. Prostheses were all single crowns. In all cases, a spiral implant 2–4 mm longer than the residual bone was placed. Only two implants were lost due to peri-implantitis but subsequently replaced and followed-up. Bone loss values around the implants after three months (at the re-opening) ranged from 0 to 0.6 mm, (median value: 0.1 mm), while after two years, the same values ranged from 0.4 to 1.3 mm (median value: 0.7 mm). Clinical post-operative complications did not occur. After ten years, no implant has been lost. Overall, the described protocol seems to show good results in terms of predictability and patient compliance

Anatomical Characteristics Of Intrapetrous Carotid Artery : A 3d Segmentation Study On Head Ct-Scan

The intrapetrous portion of internal carotid artery (IPCA) is one of the most unexplored anatomical regions, and its three-dimensional reconstruction in living subjects is still missing. The present study aims at describing IPCA on 3D models extracted from head CT-scans. The intrapetrous carotid artery was manually segmented on head CT-scans of 100 healthy patients free from vascular and neurological pathologies (50 males and 50 females aged between 18 and 91 years). Angles of the posterior and anterior genu, diameter and length of the horizontal portion, and volume of the entire canal were calculated through VAM\uae software. Statistically significant differences according to sex and side were assessed through two-way ANOVA test (p<0.05). Correlation of each measurement with age was calculated as well. On average the angles of the posterior and anterior genu were 120.1\ub110.4\ub0 and 118.0\ub110.0\ub0 in males, 119.5\ub19.2\ub0 and 117.6\ub110.3\ub0 in females, respectively, without statistically significant differences according to sex or side (p>0.05). Average length and diameter of the horizontal part were respectively 25.5\ub12.9 mm and 5.8\ub10.8 mm in males, 24.0\ub12.3 mm and 5.3\ub10.8 mm in females. The volume of IPCA was 0.941\ub10.215 cm3 in males, and 0.752\ub10.159 cm3 in females. Length and diameter of horizontal portion, and volume of IPCA showed statistically significant differences according to sex (p<0.05). No correlation with age was found. This study first provided data concerning not only linear and angular measurements, but also volumes of IPCA, useful in planning surgical interventions of the cranial base

Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand

Kit ligand (KL) is a survival factor and a mitogenic stimulus for differentiating spermatogonia. However, it is not known whether KL also plays a role in the differentiative events that lead to meiotic entry of these cells. We performed a wide genome analysis of difference in gene expression induced by treatment with KL of spermatogonia from 7-day-old mice, using gene chips spanning the whole mouse genome. The analysis revealed that the pattern of RNA expression induced by KL is compatible with the qualitative changes of the cell cycle that occur during the subsequent cell divisions in type A and B spermatogonia, i.e. the progressive lengthening of the S phase and the shortening of the G2/M transition. Moreover, KL up-regulates in differentiating spermatogonia the expression of early meiotic genes (for instance: Lhx8, Nek1, Rnf141, Xrcc3, Tpo1, Tbca, Xrcc2, Mesp1, Phf7, Rtel1), whereas it down-regulates typical spermatogonial markers (for instance: Pole, Ptgs2, Zfpm2, Egr2, Egr3, Gsk3b, Hnrpa1, Fst, Ptch2). Since KL modifies the expression of several genes known to be up-regulated or down-regulated in spermatogonia during the transition from the mitotic to the meiotic cell cycle, these results are consistent with a role of the KL/kit interaction in the induction of their meiotic differentiation

Atm reactivation reverses ataxia telangiectasia phenotypes in vivo

Hereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease

SOHLH1 and SOHLH2 control Kit expression during postnatal male germ cell development

How Kit expression is regulated in the germline remains unknown. SOHLH1 and SOHLH2, two bHLH transcription factors specifically expressed in germ cells, are involved in spermatogonia and oocyte differentiation. In the male, deletion of each factor causes loss of Kit-expressing spermatogonia in the prepuberal testis. In the female, SOHLH1 and SOHLH2 ablations cause oocyte loss in the neonatal ovary. To investigate whether Kit expression is regulated by these two factors in male germ cells, we examined SOHLH1 and SOHLH2 expression during fetal and postnatal mouse development. We found a strong positive correlation between Kit and the two transcription factors only in postnatal spermatogonia. SOHLH2 was enriched in undifferentiated spermatogonia, whereas SOHLH1 expression was maximal at Kit-dependent stages. Expression of SOHLH1, but not SOHLH2, was increased in postnatal mitotic germ cells by treatment with all-trans retinoic acid. We found that E-box sequences within the Kit promoter and its first intron can be transactivated in transfection experiments overexpressing Sohlh1 or Sohlh2. Co-transfection of both factors showed a cooperative effect. EMSA experiments showed that SOHLH1 and SOHLH2 can independently and cooperatively bind an E-box-containing probe. In vivo co-immunoprecipitations indicated that the two proteins interact and overexpression of both factors increases endogenous Kit expression in embryonic stem cells. SOHLH1 was found by ChIP analysis to occupy an E-box-containing region within the Kit promoter in spermatogonia chromatin. Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression