Development of methods of male contraception: impact of the World Health Organization Task Force

Objective: To give an historical record of the research of the World Health Organization (WHO) Task Force to develop methods of male contraception; to examine the social, political, medical, pharmaceutical, funding, and other factors that influenced progress; and to suggest reasons why such methods are only now becoming available. Design: Review of basic and clinical research over 30 years. Setting: Task force of a multinational agency and collaborating agencies. Conclusion(s): Through the involvement of many international scientists, the WHO Task Force has uniquely contributed to the exploratory phases of the research in male contraception and by its multicenter contraceptive efficacy studies has accelerated progress towards the ideal hormonal method. Despite an adverse climate involving social and political attitudes, funding constraints, and pharmaceutical industry hesitations, WHO formed coalitions with governments and international agencies to sustain research with results that apply to men in culturally diverse populations and thereby to influence activities across the whole range of global reproductive health and family planning.

Analysis of the genetic interactions between Cyclin A1, Atm and p53 during spermatogenesis

Aim： To analyze the functional interactions of Cyclin with p53 and Atm in spermatogenesis and DNA double- strand break repair. Methods： Two lines of double knockout mice were generated. Spermatogenesis and double strand break repair mechanisms were analyzed in Cyclin A1 （Ccnal）; p53- and Ccnal; Atm-double knockout mice. Results： The block in spermatogenesis observed in Cyclin A1-/- （Ccnal-/-） testes at the mid-diplotene stage is associated with polynucleated giant cells. We found that Ccnal-deficient testes and especially the giant cells accumulate unrepaired DNA double-strand breaks, as detected by immunohistochemistry for phosphorylated H2AX. In addition, the giant cells escape from apoptosis. The development of giant cells occurred in meiotic prophase I, because testes lacking ATM, which are known to develop spermatogenic arrest earlier than prophase I, do not develop giant cells in the absence of cyclin A1. Cyclin A1 interacted with p53 and phosphorylated p53 in complex with CDK2. Interestingly, p53-deficiency significantly increased the number of giant cells in Ccnal-deficient testes. Gene expression analyses of a panel of DNA repair genes in the mutant testes revealed that none of the genes examined were consistently misregulated in the absence of cyclin A1. Conclusion： Ccnal-deficiency in spermatogenesis is associated with defects in DNA double-strand break repair, which is enhanced by loss of p53.

High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson's disease

AIM： To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson＇s disease （WD） in Lithuania. METHODS： Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction （PCR） technique was used to detect the c.3207C〉A （p.H1069Q） mutation. Patients not homozygous for the c.3207C〉A （p.H1069Q） mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler （Biometra T3 Thermocycler, G0ttingen, Germany）. Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer （Applied Biosystems, Darmstadt, Germany）. RESULTS： Total of 13 WD patients （mean age 26.4 years; range 17-40; male/female 3/10） presented with hepatic disorders and 16 their first degree relatives （including 12 siblings） were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders （hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2）. Liver biopsy specimens were available in all of 13 WD patients （8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-1iver steatosis）. Twelve of 13 （92.3%） WD patients had the c.3207C〉A （p.HI069Q） mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C〉T （p.RI041W） or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder （Leipzig score 6）, no mutations were found. Out of 16 first degree WD relatives, 11 （68.7%） were heterozygous for the c.3207C〉A （p.H1069Q） mutation. Two patients with fulminant WD died from acute liver failure and ii are in full remission under peniciilamine or zinc acetate treatment. Three women with WD successfully delivered healthy babies. CONCLUSION： The c.3207C〉A （p.HI069Q） missense mutation is the most characteristic mutation for Lithuanian patients with WD. Even 92.3% of WD patients with hepatic presentation of the disease are homozygous or compound heterozygotes for the p.H1069Q mutation.

Evaluation of Landsat 7 ETM＋ Data for Spectral Discrimination and Classification of Sugarcane Varieties in Colombia

The identification of sugarcane varieties through remote sensing is studied to reduce the time taken to identify in the field, also is useful to identify non-certified varieties and to monitor the adoption of new varieties. The purpose of this study is to evaluate the Landsat 7 ETM＋ images to discriminate varieties CC85-92 and CC84-75 in the Cauca river valley in Colombia. The method used to measure the spectral separability between varieties was Jeffries-Matusita. The results indicated that the only period where a clear discrimination of the varieties is between 4th and 5th months, with a global precision of 80.8% and kappa index 0.62. The proposed methodology and preliminary results show that remote sensing is a useful tool for monitoring and identification of varieties and could be used for identification of varieties already registered and planted in other countries without the consent of their true creators.

Minutes of the 5th Meeting of the International Networ for Young Researchers in Male Fertility

The International Network for Young Researchers in Male Fertility （INYRMF; http：//www.youngresearcher.eu） is committed to establish global networks among young （early stage） scientists in testicular research and to promote collaboration and exchange of methodologies and expertise. We provide a more informal way of commu- nication than many other congresses and meetings and promote online discussions on the homepage and during our annual meetings.

More than eight years＇ hands-on experience with the novel long-acting parenteral testosterone undecanoate

Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.

Novel MLH1 frameshift mutation in an extended hereditary nonpolyposis colorectal cancer family

AIM： To present novel frameshift mutation c.31delC [p.L11X] in the MLH1 gene identified in an extended Bulgarian hereditary non-polyposis colorectal cancer （HNPCC） family and to analyze the molecular and clinical findings within the pedigree concerning the proposal of adequate individual prophylactic strategy for all mutation carriers.METHODS： The pedigree of the family consists of 42 members in four generations. Search for mutations in the MLH1 and hMSH2 genes was performed in the proband. After PCR amplification of all exons including flanking intronic regions, amplicons were directly sequenced.RESULTS： The mutation was found in nine from the thirteen pedigree members who signed informed consent to participate in the study. In three adenocarcinomas, microsatellite instability and lack of the MLH1 protein expression were detected. The only one tubulovillous adenoma analyzed was microsatellite stable and the MLH1 protein showed an intact staining.CONCLUSION： The newly described mutation c.31delC is HNPCC causative. Besides the typical clinical features of the syndrome, we found a specific pathologic manifestation such as moderate to high differentiated adenocarcinomas of the colon. One of the mutation carriers developed a benign giant cell soft tissue tumor, The primary tumor Iocalizatlons were frequently extracolonic and detailed yearly gastrointestinal and gynecological examinations have been proposed to the mutation carriers. We emphasize the importance of including the HNPCC genetic counseling and testing as well in the following surveillance of all patients at risk in the services covered by the health insurance in Bulgaria.

Thickness determination of MoS2,MoSe2,WS2 and WSe2 on transparent stamps used for deterministic transfer of 2D materials

Here,we propose a method to determine the thickness of the most common transition metal dichalcogenides (TMDCs) placed on the surface of transparent stamps,used for the deterministic placement of two-dimensional materials,by analyzing the red,green and blue channels of transmission-mode optical microscopy images of the samples.In particular,the blue channel transmittance shows a large and monotonic thickness dependence,making it a very convenient probe of the flake thickness.The method proves to be robust given the small flake-to-flake variation and the insensitivity to doping changes of MoS2.We also tested the method for MoSe2,WS2 and WSe2.These results provide a reference guide to identify the number of layers of this family of materials on transparent substrates only using optical microscopy.

Evaluation of Fire Service Command Unit Trainings

The lack of routine and training of command units and emergency managers is among the main causes of suboptimal decisions and could lead to serious consequences.To ensure optimal standards of emergency management training,specific and valid evaluation tools are needed—but are lacking.Thus,the present study’s purpose is to validate instruments for the evaluation of tactical and strategic leader trainings,in particular command unit trainings,based on survey data of n=288 German Command Unit members.Resulting questionnaires were named"FIRE-CU"(Feedback Instrument for Rescue forces Education–Command Unit)and"FIRE-CPX"(Feedback Instrument for Rescue forces Education-Command Post e Xercise scale).Results of confirmatory factor analyses show a good fit for the postulated four-dimensional structure of process scales in the FIRE-CU(trainer’s behavior,structure,overextension,group),for the two-dimensional structure of outcome scales in the FIRE-CU(self-rated competence,transfer),and for the one-dimensional structure of the FIRE-CPX.Further,strong evidence is found for reliability as well as for convergent,divergent,and concurrent validity of both the FIRE-CU and FIRE-CPX.Implications for research and practical application are also discussed to enable broad applicability in various educational programs for public security and crisis management.

Correction to:Evaluation of Fire Service Command Unit Trainings

Correction to:Int J Disaster Risk Sci(2020)11:300-315 https://doi.org/10.1007/s13753-020-00279-6 In the notes to figures 1 to 3 in our article“Evaluation of Fire Service Command Unit Trainings”(Thielsch and Hadzihalilovic 2020)it was incorrectly stated that standardized coefficients were shown.In fact,however,the non-standardized coefficients appear in these figures.We apologize for the mistake in the illustration!It is important to note that the results of the factor analyses do not change.The corrected figures can be found online at https://doi.org/10.5281/zenodo.4643373,we recommend using them in case of a presentation of our results.

Evidence of active oviposition avoidance to systemically applied imidacloprid in the Colorado potato beetle

Agricultural pests can develop behavioral resistance to insecticides by choosing to feed or oviposit on insecticide-free hosts.As young larvae have relatively low mobility,oviposition preferences from female adults may play a critical role in shaping the evolu-tionary trajectory of pest populations.While oviposition avoidance of insecticide-treated hosts was found in different agriculture pests,it remains unclear whether female adults actively choose to occupy insecticide-free hosts.To address this question,we investigated feeding and oviposition preferences between imidacloprid-treated and imidacloprid-free plants in the Colorado potato beetle,Leptinotarsa decemlineata Say,a major potato pest.We performed behavioral choice assays on two strains that differed in both fecundity and insecticide resistance.We found that one strain preferred to feed on the insecticide-free plants and that this preference is not innate.Meanwhile,the other strain chose plants for feeding and oviposition randomly.Further analyses of the moving patterns of the beetles suggested that the oviposition preference in the first strain is likely due to active learning.

Mate assessment behavior is correlated to learning ability in female threespine sticklebacks

In many species, males signal quality with elaborate traits, but females often show inter-individual variation in pref ere nee for these traits. Choosi ng a mate requires multiple cog nitive steps;therefore, cog nitive style (how an in dividual processes information) likely in fluences the perception of sexual signals and ability to choose a high-quality mate. An important component of cognitive style is flexibility;cognitively flexible individuals are more perceptive to shifts in cues. We hypothesized that cognitively flexible individuals would acquire more information about potential mates, better discern between two quality-signaling traits, and thus be more discriminatory. Here, we show that mate assessment is correlated to other cognitive traits. Although we did not detect an effect of cogn itive style on mate pref ere nee or discriminatio n, we found that female threespi ne sticklebacks Gasterosteus aculeatus that spent more time assessing potential mates (more responsive) in a dichotomous mate choice task reached both the initial and reversal learning criterion in a spatial learning task with fewer errors. However, these highly responsive females made more consecutive mistakes immediately at the beginning of the reversal phase, suggest!ng that they did not quickly adapt to the en vironmental cha nge but in stead rapidly formed strict routi nes duri ng the learning task that were eventually reversible after repeated errors. Furthermore, we found evidenee for condition-dependent mate pref ere nee, with larger females preferring the high-quality male. These are among the first results that illustrate how cog nitive traits might in flue nee mate choice, which has implicati ons for the st re ngth and di recti on of sexual selection.

Simulating small-scale climate change effects-lessons from a short-term field manipulation experiment on grassland arthropods

Climate change is expected to cause major consequences on biodiversity. Understanding species-specific reactions, such as species shifts, species declines, and changes in population dynamics is a key issue to quantify large-scale impacts of climate change on biotic communities. As it is often impossible or at least impracticable to conduct large-scale experiments on biotic responses to climate change, studies at a smaller scale may be a useful alternative. In our study, we therefore tested responses of grassland arthropods （carabid beetles, spiders, grasshoppers） to simulated climate change in terms of species activity densities and diversity. We conducted a controlled field experiment by changing water and microclimatic conditions at a small scale （16 m2）. Roof constructions were used to increase drought-like conditions, whereas water supply was enhanced by irrigation. In all, 2 038 carabid beetles （36 species）, 4 893 spiders （65 species）, and 303 Orthoptera （4 species） were caught using pitfall traps from May to August, 2010. During our experiment, we created an artificial small-scale climate change; and statistics revealed that these changes had short-term effects on the total number of individuals and Simpson diversity of the studied arthropod groups. Moreover, our results showed that certain species might react very quickly to climate change in terms of activity densities, which in turn might influence diversity due to shifts in abundance patterns. Finally, we devised methodological improvements that may further enhance the validity of future studies.

Getting lost in the weeds:How VVQX9 has shed light on gene functional divergence

Studying functional divergence between different species is key to understanding gene evolution,but it is challenging when comparison of distant phyla or when allelic diversity is limiting.

bHLH Root Hair Booster in Low-Phosphate Conditions

Phosphorus is a macronutrient essential for many crucial plant biological processes including photosynthesis.To cope with the limited availability of phosphate(Pi)in the soil,plants have developed multiple strategies including increased hair root density to acquire this immobile nutrient.However,the precise molecular mechanisms underlying such strategies have not been fully elucidated.

The Bigger the Merrier:TERMINAL FLOWER 1 Protein Movement Controls Seed Size

Increasing seed size is an efficient way to improve crop yield.In flowering plants,following double fertilization the rapid growth of the integument and endosperm generates a large cavity in the seed.After the syncytial phase,the syncytium divides into individual cells resulting in the cellularization of the endosperm.The volume available for the subsequent embryo development and thus seed size,is directly linked to the timing of endosperm cellularization.If cellularization occurs precociously,the seed will be smaller and vice versa.

A RESTful proxy and data model for linked sensor data

The vision of a Digital Earth calls for more dynamic information systems,new sources of information,and stronger capabilities for their integration.Sensor networks have been identified as a major information source for the Digital Earth,while Semantic Web technologies have been proposed to facilitate integration.So far,sensor data are stored and published using the Observations&Measurements standard of the Open Geospatial Consortium(OGC)as data model.With the advent of Volunteered Geographic Information and the Semantic Sensor Web,work on an ontological model gained importance within Sensor Web Enablement(SWE).In contrast to data models,an ontological approach abstracts from implementation details by focusing on modeling the physical world from the perspective of a particular domain.Ontologies restrict the interpretation of vocabularies toward their intended meaning.The ongoing paradigm shift to Linked Sensor Data complements this attempt.Two questions have to be addressed:(1)how to refer to changing and frequently updated data sets using Uniform Resource Identifiers,and(2)how to establish meaningful links between those data sets,that is,observations,sensors,features of interest,and observed properties?In this paper,we present a Linked Data model and a RESTful proxy for OGC’s Sensor Observation Service to improve integration and inter-linkage of observation data for the Digital Earth.

StarFL - a modularised metadata language for sensor descriptions

An ever-increasing number of sensor resources are being exposed via the World Wide Web to become part of the Digital Earth.Discovery,selection and use of these sensors and their observations require a robust sensor information model,but the consistent description of sensor metadata is a complex and difficult task.Currently,the only available robust model is SensorML,which is intentionally designed in a very generic way.Due to this genericness,interoperability can hardly be achieved without the definition of application profiles that further constrain the use and expressiveness of the root language.So far,such SensorML profiles have only been developed up to a limited extent.This work describes a new approach for defining sensor metadata,the Starfish Fungus Language(StarFL)model.This language follows a more restrictive approach and incorporates concepts from the recently published Semantic Sensor Network Ontology to overcome the key issues users are experiencing with SensorML.StarFL defines a restricted vocabulary and model for sensor metadata to achieve a high level of interoperability and a straightforward reusability of sensor descriptions.

Discourse Strategies in President Buhari's Speech on the#EndSARS Protests in Nigeria

This article examines the discursive strategies employed to negotiate power and ideology in President Buhari’s speech on the#EndSARS Protests in Nigeria.The data for the study comprises President Muhammadu Buhari’s speech on the#EndSARS protests.The speech was analysed using both Systemic Functional Linguistics and Critical Discourse Analysis,and a discussion of how transitivity patterns and modality choices explain the representation of power,ideology and dominance in the speech followed.The findings of the study show that the transitivity and modality systems used by the president revealed his disposition toward the participants involved in the protests,and his perception of himself in relation to the others:whether they take an active or passive role in the discourse.The paper concludes that transitivity patterns and modality structures can be used to highlight social actors who on the surface appear common and natural,when they essentially perpetuate inequality and injustice.