Rotational motion and rheotaxis of human sperm do not require functional CatSper channels and transmembrane Ca2+ signaling.

Navigation of sperm in fluid flow, called rheotaxis, provides long-range guidance in the mammalian oviduct. The rotation of sperm around their longitudinal axis (rolling) promotes rheotaxis. Whether sperm rolling and rheotaxis require calcium (Ca2+ ) influx via the sperm-specific Ca2+ channel CatSper, or rather represent passive biomechanical and hydrodynamic processes, has remained controversial. Here, we study the swimming behavior of sperm from healthy donors and from infertile patients that lack functional CatSper channels, using dark-field microscopy, optical tweezers, and microfluidics. We demonstrate that rolling and rheotaxis persist in CatSper-deficient human sperm. Furthermore, human sperm undergo rolling and rheotaxis even when Ca2+ influx is prevented. Finally, we show that rolling and rheotaxis also persist in mouse sperm deficient in both CatSper and flagellar Ca2+ -signaling domains. Our results strongly support the concept that passive biomechanical and hydrodynamic processes enable sperm rolling and rheotaxis, rather than calcium signaling mediated by CatSper or other mechanisms controlling transmembrane Ca2+ flux

Identificación y análisis de los recursos económicos asignados a la segunda locomotora. Evolución, aciertos y desaciertos

Con la elaboración del presente documento, se pretende identificar y analizar los recursos económicos asignados a una de las locomotoras del gobierno del presidente Juan Manuel Santos en el marco de su plan de desarrollo Prosperidad para todos y el impacto social de esta asignación de recursos en el agro Colombiano, Así mismo evaluar el cumplimiento de dicha política publica y la generación de bienestar social en la población."With the production of the present document, one tries to identify and to analyze the economic resources assigned to one of the locomotives of the government of the president Juan Manuel Santos in the frame of his plan of development "" Prosperity for all "" and the social impact of this assignment of resources in the Colombian agro, Likewise to evaluate the fulfillment of the above mentioned politics publishes and the generation of social well-being in the population.

[3]Ferrocenophanes with a tetramethyldisiloxane bridge: synthesis and molecular structure

Siemeling U, Krallmann R, Jutzi P, Neumann B, Stammler H-G. [3]Ferrocenophanes with a tetramethyldisiloxane bridge: synthesis and molecular structure. Monatshefte für Chemie. 1994;125(5):579-586.6,6,8,8-Tetramethyl-7-oxa-6,8-disila[3]-ferrocenophan 2 entsteht aus dem Di(alkoxysilyl)ferrocen (H4C5SiMe2OR)2Fe (R=CH2CH2OCH2CH2OCH2CH2OMe) durch Hydrolyse und anschließende intramolekulare Disiloxan-Bildung. 2,2',3,3',4,4',5,5',6,6,8,8-Dodecamethyl-7-oxa-6,8-disila[3]ferrocenophan 3 wurde durch Luftoxidation von 2,2',3,3',4,4',5,5',6,6,7,7-Dodecamethyl-6,7-disila[2]ferrocenophan erhalten. Die Kristallstrukturen beider Verbindungen wurden durch Einkristall-Röntgenstrukturanalyse bestimmt (2:a=8.5330(10), b=15.610(3), c=18.774(5)Å, [alpha]=70.68(2), [beta]=77.94(2), [gamma]=75.150(10)°, V=2259.8(8)Å3, Z=6, Raumgruppe P1, R=0.045, Rw =0.044; 3:a=12.388(3), b=9.924(3), c=19.136(10)Å, [beta]=105.11(3)°, V=2271.2(15)Å3, Z=4, Raumgruppe P21/c, R=0.076, Rw =0.060). Wegen der Flexibilität der Disiloxan-Brücke sind 2 und 3 ungespannte Moleküle

Economic Scheduling in Grid Computing

Grid computing is a promising technology for future computing platforms. Here, the task of scheduling computing resources proves difficult as resources are geographically distributed and owned by individuals with different access and cost policies. This paper addresses the idea of applying economic models to the scheduling task. To this end a scheduling infrastructure and a market-economic method is presented. The efficiency of this approach in terms of response- and wait-time minimization as well as utilization is evaluated by simulations with real workload traces. The evaluations show that the presented economic scheduling algorithm provides similar or even better average weighted response-times as common algorithms like backfilling. This is especially promising as the presented economic models have additional advantages as e.g. support for different price models, optimization objectives, access policies or quality of service demands

Scaling of workload traces

Abstract — The design and evaluation of job scheduling strategies often require simulations with workload data or models. Usually workload traces are the most realistic data source as they include all explicit and implicit job patterns which are not always considered in a model. In this paper, a method is presented to enlarge and/or duplicate jobs in a given workload. This allows the scaling of workloads for later use on parallel machine configurations with a different number of processors. As quality criteria the scheduling results by common algorithms have been examined. The results show high sensitivity of schedule attributes to modifications of the workload. To this end, different strategies of scaling number of job copies and/or job size have been examined. The best results had been achieved by adjusting the scaling factors to be higher than the precise relation between the new scaled machine size and the original source configuration. I

Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes

STUDY QUESTION: Do bi-allelic variants in the genes encoding the MSH4/MSH5 heterodimer cause male infertility? SUMMARY ANSWER: We detected biallelic, (likely) pathogenic variants in MSH5 (4 men) and MSH4 (3 men) in six azoospermic men, demonstrating that genetic variants in these genes are a relevant cause of male infertility. WHAT IS KNOWN ALREADY: MSH4 and MSH5 form a heterodimer, which is required for prophase of meiosis I. One variant in MSH5 and two variants in MSH4 have been described as causal for premature ovarian insufficiency (POI) in a total of five women, resulting in infertility. Recently, pathogenic variants in MSH4 have been reported in infertile men. So far, no pathogenic variants in MSH5 had been described in males. STUDY DESIGN, SIZE, DURATION: We utilized exome data from 1305 men included in the Male Reproductive Genomics (MERGE) study, including 90 males with meiotic arrest (MeiA). Independently, exome sequencing was performed in a man with MeiA from a large consanguineous family. PARTICIPANTS/MATERIALS, SETTING, METHODS: Assuming an autosomal-recessive mode of inheritance, we screened the exome data for rare, biallelic coding variants in MSH4 and MSH5. If possible, segregation analysis in the patients' families was performed. The functional consequences of identified loss-of-function (LoF) variants in MSH5 were studied using heterologous expression of the MSH5 protein in HEK293T cells. The point of arrest during meiosis was determined by γH2AX staining. MAIN RESULTS AND THE ROLE OF CHANCE: We report for the first time (likely) pathogenic, homozygous variants in MSH5 causing infertility in 2 out of 90 men with MeiA and overall in 4 out of 902 azoospermic men. Additionally, we detected biallelic variants in MSH4 in two men with MeiA and in the sister of one proband with POI. γH2AX staining revealed an arrest in early prophase of meiosis I in individuals with pathogenic MSH4 or MSH5 variants. Heterologous in vitro expression of the detected LoF variants in MSH5 showed that the variant p.(Ala620GlnTer9) resulted in MSH5 protein truncation and the variant p.(Ser26GlnfsTer42) resulted in a complete loss of MSH5. LARGE SCALE DATA: All variants have been submitted to ClinVar (SCV001468891-SCV001468896 and SCV001591030) and can also be accessed in the Male Fertility Gene Atlas (MFGA). LIMITATIONS, REASONS FOR CAUTION: By selecting for variants in MSH4 and MSH5, we were able to determine the cause of infertility in six men and one woman, leaving most of the examined individuals without a causal diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings have diagnostic value by increasing the number of genes associated with non-obstructive azoospermia with high clinical validity. The analysis of such genes has prognostic consequences for assessing whether men with azoospermia would benefit from a testicular biopsy. We also provide further evidence that MeiA in men and POI in women share the same genetic causes. STUDY FUNDING/COMPETING INTEREST(S): This study was carried out within the frame of the German Research Foundation sponsored Clinical Research Unit 'Male Germ Cells: from Genes to Function' (DFG, CRU326), and supported by institutional funding of the Research Institute Amsterdam Reproduction and Development and funds from the LucaBella Foundation. The authors declare no conflict of interest

Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes

STUDY QUESTION: Do bi-allelic variants in the genes encoding the MSH4/MSH5 heterodimer cause male infertility? SUMMARY ANSWER: We detected biallelic, (likely) pathogenic variants in MSH5 (4 men) and MSH4 (3 men) in six azoospermic men, demonstrating that genetic variants in these genes are a relevant cause of male infertility. WHAT IS KNOWN ALREADY: MSH4 and MSH5 form a heterodimer, which is required for prophase of meiosis I. One variant in MSH5 and two variants in MSH4 have been described as causal for premature ovarian insufficiency (POI) in a total of five women, resulting in infertility. Recently, pathogenic variants in MSH4 have been reported in infertile men. So far, no pathogenic variants in MSH5 had been described in males. STUDY DESIGN, SIZE, DURATION: We utilized exome data from 1305 men included in the Male Reproductive Genomics (MERGE) study, including 90 males with meiotic arrest (MeiA). Independently, exome sequencing was performed in a man with MeiA from a large consanguineous family. PARTICIPANTS/MATERIALS, SETTING, METHODS: Assuming an autosomal-recessive mode of inheritance, we screened the exome data for rare, biallelic coding variants in MSH4 and MSH5. If possible, segregation analysis in the patients' families was performed. The functional consequences of identified loss-of-function (LoF) variants in MSH5 were studied using heterologous expression of the MSH5 protein in HEK293T cells. The point of arrest during meiosis was determined by γH2AX staining. MAIN RESULTS AND THE ROLE OF CHANCE: We report for the first time (likely) pathogenic, homozygous variants in MSH5 causing infertility in 2 out of 90 men with MeiA and overall in 4 out of 902 azoospermic men. Additionally, we detected biallelic variants in MSH4 in two men with MeiA and in the sister of one proband with POI. γH2AX staining revealed an arrest in early prophase of meiosis I in individuals with pathogenic MSH4 or MSH5 variants. Heterologous in vitro expression of the detected LoF variants in MSH5 showed that the variant p.(Ala620GlnTer9) resulted in MSH5 protein truncation and the variant p.(Ser26GlnfsTer42) resulted in a complete loss of MSH5. LARGE SCALE DATA: All variants have been submitted to ClinVar (SCV001468891-SCV001468896 and SCV001591030) and can also be accessed in the Male Fertility Gene Atlas (MFGA). LIMITATIONS, REASONS FOR CAUTION: By selecting for variants in MSH4 and MSH5, we were able to determine the cause of infertility in six men and one woman, leaving most of the examined individuals without a causal diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings have diagnostic value by increasing the number of genes associated with non-obstructive azoospermia with high clinical validity. The analysis of such genes has prognostic consequences for assessing whether men with azoospermia would benefit from a testicular biopsy. We also provide further evidence that MeiA in men and POI in women share the same genetic causes. STUDY FUNDING/COMPETING INTEREST(S): This study was carried out within the frame of the German Research Foundation sponsored Clinical Research Unit 'Male Germ Cells: from Genes to Function' (DFG, CRU326), and supported by institutional funding of the Research Institute Amsterdam Reproduction and Development and funds from the LucaBella Foundation. The authors declare no conflict of interest