CABYR is essential for fibrous sheath integrity and progressive motility in mouse spermatozoa

Ca²⁺-binding tyrosine-phosphorylation-regulated protein (CABYR) has been implicated in sperm physiological function in several in vitro studies. It has also been implicated as a potential cause of and diagnostic tool in asthenozoospermic human males. CABYR is known to be localized to the fibrous sheath, an accessory structure in the flagellar principal piece. Utilizing the CRISPR–Cas9 technology, we have knocked out this gene in mice to understand its role in male fertility. <i>Cabyr</i>-knockout male mice showed severe subfertility with a defect in sperm motility as well as a significant disorganization in the fibrous sheath. Further, abnormal configuration of doublet microtubules was observed in the Cabyr-knockout spermatozoa, suggesting that the fibrous sheath is important for the correct organization of the axoneme. Our results show that it is the role of CABYR in the formation of the fibrous sheath that is essential for male fertility

Evidence that Fetal Death is Associated with Placental Aging

Background: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. Objective: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. Study Design: We collected placentas from women at 37-39 weeks’ gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Results: Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. Conclusion: Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue

Men's Preconception Health: A Primary Health-Care Viewpoint

The purpose of this article is to theoretically explore men’s preconception health as a mechanism to enhance fertility, as well as the health and well-being of the subject and his descendants. Premorbid risk factors and behaviors associated with stress, environmental toxins, excessive alcohol consumption, smoking, lack of exercise/obesity, and the use of illicit drugs are all known to affect fecundity. While there are many health clinics available to women, where advice in areas such as postnatal care of the newborn, family planning, and couples fertility is provided, there are few, if any, equivalent health clinics available to men. Additionally, getting men to attend primary health-care services has also been continuously problematic, even in the context of there being a clearly discernible need for treatment. It is argued in this article that an impetus is required to encourage men to focus on and improve their preconception health and to utilize primary health-care services to take action. An assertive men’s preconception health outlook can positively influence the conjugal relationship, fathering, male self-esteem, and continued good health. Using the sometimes complex concept of preconception health as a motivating factor for healthy lifestyle adaptation has the potential to improve male fertility outcomes and general health and well-being, as well as the health of future generations

Re-Forming vision. On the governmentality of Griersonian documentary film

© 2015 Taylor & Francis. This essay traces and discusses John Grierson\u27s programme for documentary film and its projected function and operation within liberal democracy. It is argued that documentary film as envisioned and propagated by Grierson neither set out to advance \u27open\u27 and/or controversial public discourse \u27from an Enlightenment standpoint\u27 (Rosen, Philip. 2001. Change Mummified: Cinema, Historicity, Theory. Minneapolis: University of Minnesota Press, 249) nor to educate its popular audiences through the dissemination of facts. As such Griersonian documentary film should be less located within the pedagogical tradition of the Enlightenment and was not to mainly function as a \u27discourse of sobriety\u27 (Nichols, Bill. 1991. Representing Reality: Issues and Concepts in Documentary. Bloomington: Indiana University Press). Rather, it was to insensibly shape subjectivities and agents by strategically arranging \u27visions of the real\u27. Documentary set out to model what Grierson termed \u27the subconscious\u27, the implicit framework that shaped citizen\u27s thoughts, desires, emotions and agency by which they governed their selves, others and by extension society at large into the future. Grierson\u27s documentary programme decisively governmentalised so-called non-fiction film as a specific technique of democratic government. It sought to render the formative and \u27creative\u27 aspects of its production transparent in favour of effect through affect by shaping appropriate visions for a reality yet to become. Thereby Grierson\u27s programme set out to strategically subjectify popular audiences/\u27ordinary citizens\u27 towards a desirable and \u27better\u27 national and global future

Ocular late effects in childhood and adolescent cancer survivors: A report from the childhood cancer survivor study

Introduction—Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors. Procedure—The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of 6 ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings. Results—Five or more years from the diagnosis, survivors were at increased risk of cataracts (RR:10.8; 95% CI: 6.2–18.9), glaucoma (RR: 2.5; 95% CI: 1.1–5.7), legal blindness (RR: 2.6; 95% CI: 1.7–4.0), double vision (RR:4.1; 95% CI: 2.7–6.1), and dry eyes (RR: 1.9; 95% CI: 1.6–2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose-dependent fashion. Risk of cataracts were also associated with radiation 3000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0–14.3), temporal lobe (RR: 9.4; 95% CI: 5.6–15.6), and exposure to prednisone (RR:2.3; 95% CI:.1.6–3.4) Conclusions—Childhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long-term follow-up is needed to evaluate potential progression of ocular deficits and impact on quality of life

Yellow Fever Virus Infectivity for Bolivian Aedes aegypti Mosquitoes

The absence of urban yellow fever virus (YFV) in Bolivian cities has been attributed to the lack of competent urban mosquito vectors. Experiments with Aedes aegypti from Santa Cruz, Bolivia, demonstrated infection (100%), dissemination (20%), and transmission of a Bolivian YFV strain (CENETROP-322)

Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions?

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or ‘add-ons’ that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high quality evidence that the procedure is safe and effective. Only then should the technique be considered as ‘routine’ and only when applied to the similar patient population as those studied in the RCT. Even then, further paediatric and long-term follow up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories including embryo glue and adherence compounds, sperm DNA fragmentation, time lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching and examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients