Explore the vast range of titles available.

We apply data mining to version histories in order to guide programmers along related changes: \"Programmers who changed these functions also changed...\" Given a set of existing changes, the mined association rules 1) suggest and predict likely further changes, 2) show up item coupling that is undetectable by program analysis, and 3) can prevent errors due to incomplete changes. After an initial change, our ROSE prototype can correctly predict further locations to be changed; the best predictive power is obtained for changes to existing software. In our evaluation based on the history of eight popular open source projects, ROSE's topmost three suggestions contained a correct location with a likelihood of more than 70 percent.

Non-mammalian vertebrates have an intrinsically photosensitive iris and thus a local pupillary light reflex (PLR). In contrast, it is thought that the PLR in mammals generally requires neuronal circuitry connecting the eye and the brain. Here we report that an intrinsic component of the PLR is in fact widespread in nocturnal and crepuscular mammals. In mouse, this intrinsic PLR requires the visual pigment melanopsin; it also requires PLCβ4, a vertebrate homologue of the Drosophila NorpA phospholipase C which mediates rhabdomeric phototransduction. The Plcb4 −/− genotype, in addition to removing the intrinsic PLR, also essentially eliminates the intrinsic light response of the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (M1-ipRGCs), which are by far the most photosensitive ipRGC subtype and also have the largest response to light. Ablating in mouse the expression of both TRPC6 and TRPC7, members of the TRP channel superfamily, also essentially eliminated the M1-ipRGC light response but the intrinsic PLR was not affected. Thus, melanopsin signalling exists in both iris and retina, involving a PLCβ4-mediated pathway that nonetheless diverges in the two locations. Mammalian pupil sees the light Contraction of the mammalian iris in response to light has been thought to require neuronal circuitry connecting the retina to the brain. Now King Yau and colleagues report the surprising observation that in a wide variety of mammals, the eye's pupil is intrinsically photosensitive. Iris muscles isolated from nocturnal mammals such as mice — but not from primates — contract when exposed to light through the action of a melanopsin-based signalling pathway that partially overlaps with its retinal counterpart. Previously, the intrinsic pupillary reflex was thought to be an exclusive property of lower vertebrates such as fish, amphibians and birds.

Agonist-induced Ca 2+ entry into cells by both store-operated channels and channels activated independently of Ca 2+ -store depletion has been described in various cell types. The molecular structures of these channels are unknown as is, in most cases, their impact on various cellular functions. Here we describe a store-operated Ca 2+ current in vascular endothelium and show that endothelial cells of mice deficient in TRP4 (also known as CCE1) lack this current. As a consequence, agonist-induced Ca 2+ entry and vasorelaxation is reduced markedly, showing that TRP4 is an indispensable component of store-operated channels in native endothelial cells and that these channels directly provide an Ca 2+ -entry pathway essentially contributing to the regulation of blood vessel tone.

Zusammenfassung Koloproktologische Eingriffe stellen aufgrund der natürlichen Keimbesiedelung der betroffenen Bereiche besondere Anforderungen an die hygienischen Maßnahmen vor, während und nach der Operation. Auch wenn die normale Keimbesiedelung der Analregion durch Desinfektionsmaßnahmen nicht gänzlich beseitigt werden kann, so sollte durch die Beachtung entsprechender Empfehlungen und Leitlinien das Risiko für Infektionen oder Komplikationen auf ein Minimum reduziert werden. Bei der Durchführung von Eingriffen in kontaminierten Regionen gelten im Allgemeinen die gleichen Regeln wie bei anderen Operationen, wobei – soweit wie möglich – die Grundsätze der Asepsis zu berücksichtigen sind. Dieser Leitfaden zur Hygiene in der Koloproktologie gibt wichtige und nützliche Empfehlungen für die koloproktologische Praxis, um das Infektionsrisiko während einer proktologischen Untersuchung und Behandlung für Behandelnde, Patienten und das medizinische Personal so gering wie möglich zu halten.

Koloproktologische Eingriffe stellen aufgrund der natürlichen Keimbesiedelung der betroffenen Bereiche besondere Anforderungen an die hygienischen Maßnahmen vor, während und nach der Operation. Auch wenn die normale Keimbesiedelung der Analregion durch Desinfektionsmaßnahmen nicht gänzlich beseitigt werden kann, so sollte durch die Beachtung entsprechender Empfehlungen und Leitlinien das Risiko für Infektionen oder Komplikationen auf ein Minimum reduziert werden. Bei der Durchführung von Eingriffen in kontaminierten Regionen gelten im Allgemeinen die gleichen Regeln wie bei anderen Operationen, wobei – soweit wie möglich – die Grundsätze der Asepsis zu berücksichtigen sind. Dieser Leitfaden zur Hygiene in der Koloproktologie gibt wichtige und nützliche Empfehlungen für die koloproktologische Praxis, um das Infektionsrisiko während einer proktologischen Untersuchung und Behandlung für Behandelnde, Patienten und das medizinische Personal so gering wie möglich zu halten.

Legionella pneumophila, the causative agent of Legionnaires’ disease, is able to survive and multiply efficiently in a variety of mammalian cells. By using in vitro assays, the uptake of L. pneumophila into monocytes has shown to be mediated, at least in part, through attachment of complement-coated bacteria to complement receptors, but complement-independent phagocytosis could also be demonstrated. Since complement levels in the human lung are normally low, the role of complement-dependent phagocytosis in the pathogenesis of Legionnaires’ disease is doubtful. However, the contribution of other potential phagocytosis-related host cell surface molecules to the phagocytosis of L. pneumophila has never been investigated. We therefore analyzed the role of complement receptors 1 (CD35) and 3 (CD11b/18), the lipopolysaccharide (LPS) receptor (CD14), the β 1-integrin chain of the fibronectin receptor (CD29), the intercellular adhesion molecule 1 (ICAM-1, CD54) and the transferrin receptor (CD71) in the complement-independent uptake of L. pneumophila. To exclude any influence of culture conditions onto phagocytosis rates, we compared a fresh clinical isolate with an agar-adapted isolate of L. pneumophila. In addition, we used three different host cell types (MM6, HeLa and Jurkat cells) expressing different rates of complement receptors. We could show that both strains of L. pneumophila were phagocytized by the three host cell lines to the same extent, but intracellular multiplication was only found in MM6 and, although to a much lesser degree, in Jurkat cells. Preincubation of MM6 cells with monoclonal antibodies directed against the above cited phagocytosis-related receptors did not result in inhibition of L. pneumophila uptake. We therefore conclude that typical phagocytosis-related cell surface receptors are not involved in the complement-independent phagocytosis of L. pneumophila.

Numerous studies demonstrating that statistical errors are common in basic science publications have led to calls to improve statistical training for basic scientists. In this article, we sought to evaluate statistical requirements for PhD training and to identify opportunities for improving biostatistics education in the basic sciences. We provide recommendations for improving statistics training for basic biomedical scientists, including: 1. Encouraging departments to require statistics training, 2. Tailoring coursework to the students' fields of research, and 3. Developing tools and strategies to promote education and dissemination of statistical knowledge. We also provide a list of statistical considerations that should be addressed in statistics education for basic scientists.

Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to serious maternal and fetal complications. It is a multisystem disease that is commonly, but not always, accompanied by proteinuria. Its cause(s) remain unknown, and delivery remains the only definitive treatment. It is increasingly recognized that many pathophysiological processes contribute to this syndrome, with different signaling pathways converging at the point of systemic endothelial dysfunction, hypertension, and proteinuria. Different animal models of pre-eclampsia have proven utility for specific aspects of pre-eclampsia research, and offer insights into pathophysiology and treatment possibilities. Therapeutic interventions that specifically target these pathways may optimize pre-eclampsia management and may improve fetal and maternal outcomes. In addition, recent findings regarding placental, endothelial, and podocyte pathophysiology in pre-eclampsia provide unique and exciting possibilities for improved diagnostic accuracy. Emerging evidence suggests that testing for urinary podocytes or their markers may facilitate the prediction and diagnosis of pre-eclampsia. In this review, we explore recent research regarding placental, endothelial, and podocyte pathophysiology. We further discuss new signaling and genetic pathways that may contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic strategies, and potential targeted interventions.

Open, reproducible, and replicable research practices are a fundamental part of science. Training is often organized on a grassroots level, offered by early career researchers, for early career researchers. Buffet style courses that cover many topics can inspire participants to try new things; however, they can also be overwhelming. Participants who want to implement new practices may not know where to start once they return to their research team. We describe ten simple rules to guide participants of relevant training courses in implementing robust research practices in their own projects, once they return to their research group. This includes (1) prioritizing and planning which practices to implement, which involves obtaining support and convincing others involved in the research project of the added value of implementing new practices; (2) managing problems that arise during implementation; and (3) making reproducible research and open science practices an integral part of a future research career. We also outline strategies that course organizers can use to prepare participants for implementation and support them during this process.

Background Preeclampsia is a pregnancy-specific hypertensive disorder characterized by impaired angiogenesis. We postulate that senescence of mesenchymal stem cells (MSC), multipotent cells with pro-angiogenic activities, is one of the mechanisms by which systemic inflammation exerts inhibitory effects on angiogenesis in preeclampsia. Methods MSC were isolated from abdominal fat tissue explants removed during medically indicated C-sections from women with preeclampsia (PE-MSC, n  = 10) and those with normotensive pregnancies (NP-MSC, n  = 12). Sections of the frozen subcutaneous adipose tissue were assessed for inflammation by staining for tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1. Viability, proliferation, and migration were compared between PE-MSC vs. NP-MSC. Apoptosis and angiogenesis were assayed before and after treatment with a senolytic agent (1 μM dasatinib) using the IncuCyte S3 Live-Cell Analysis System. Similarly, staining for senescence-associated beta galactosidase (SABG) and qPCR for gene expression of senescence markers, p16 and p21, as well as senescence-associated secretory phenotype (SASP) components, IL-6, IL-8, MCP-1, and PAI-1, were studied before and after treatment with dasatinib and compared between PE and NP. Results After in vitro exposure to TNF-alpha, MSC demonstrated upregulation of SASP components, including interleukins-6 and -8 and MCP-1. Staining of the subcutaneous adipose tissue sections revealed a greater inflammatory response in preeclampsia, based on the higher levels of both TNF-alpha and MCP-1 compared to normotensive pregnancies ( p < 0.001 and 0.024, respectively). MSC isolated from PE demonstrated a lower percentage of live MSC cells ( p  = 0.012), lower proliferation ( p  = 0.005), and higher migration ( p  = 0.023). At baseline, PE-MSC demonstrated a senescent phenotype, reflected by more abundant staining for SABG ( p  < 0.001), upregulation of senescence markers and SASP components, as well as lower angiogenic potential ( p  < 0.001), compared to NP-MSC. Treatment with dasatinib increased significantly the number of apoptotic PE-MSC compared to NP-MSC (0.011 vs. 0.093) and decreased the gene expression of p16 and six SASP components. The mechanistic link between senescence and impaired angiogenesis in PE was confirmed by improved angiogenic potential of PE-MSC ( p  < 0.001) after dasatinib treatment. Conclusions Our data suggest that MSC senescence exerts inhibitory effects on angiogenesis in preeclampsia. Senolytic agents may offer the opportunity for mechanism-based therapies.