Drug transporters in spermatogenesis: A re-evaluation of recent data on P-glycoprotein

Drug transporters are integral membrane proteins expressed by a variety of organs, including the liver, kidney, small intestine and testis, and they are generally known to mediate drug or xenobiotic transport into and out of cells. Previous studies have also reported the presence of several drug transporters at blood-tissue barriers where they are thought to protect organs from harmful agents. In this editorial, we briefly discuss and re-evaluate recent findings that show P-glycoprotein, an efflux pump, to function at the blood-testis barrier. We also put forth a mechanistic model, hoping this information will form a strong basis for future studies

The adhering junction dynamics in the testis are regulated by an interplay of beta 1-integrin, focal adhesion kinase (FAK) and the focal adhesion complex (FAC)-associated proteins

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Filamin A: A regulator of blood-testis barrier assembly during post-natal development

Filamins are a family of actin-binding proteins composed of filamin A, B and C. Besides of their ability to induce perpendicular branching of F-actin filaments via their actin binding domains near the N-terminus, filamins can regulate multiple cellular functions because of their unique ability to recruit more than 90 protein binding partners to their primary sequences which are having highly diversified cellular functions. However, this family of proteins has not been examined in the testis until recently. Herein, we highlight recent findings in the field regarding the role of these proteins in cell epithelia, and based on recent data in the testis regarding their role on spermatogenesis, this review provides the basis for future functional studies

Review of Engaging Education: Developing Emotional Literacy, Equity and Co-education. Brian Matthews. (Book Review)

The book is only about a fraction of its title Engaging Education. His section on ‘engaging the emotions’ sums this up: whereas the book is largely about engaging the emotions positively, the definition of ‘Engaging’ is more far reaching: “that pupils should be involved in their learning; be active and absorbed and not just passive recipients of a set curriculum. Additionally, they should feel engaged in the processes of education and have some input into creating their own agendas for learning” (p.2). Exploring the full impact of this statement across the curriculum really needs a different book

In search of suitable in vitro models to study germ cell movement across the blood-testis barrier

The movement of preleptotene/leptotene spermatocytes across the blood-testis barrier, also known as the Sertoli cell barrier, during stages VIII to XI of the seminiferous epithelial cycle is one of the most important cellular events taking place in the mammalian testis. Without the passage of spermatocytes, spermatogenesis would be halted, resulting in transient or permanent sterility. Unfortunately, we have very little knowledge on how preleptotene/leptotene spermatocytes cross the blood-testis barrier. While we know cytokines, proteases and androgens to mediate Sertoli cell junction restructuring, most data continue to be derived from experiments using Sertoli cells cultured alone in two dimensions. Thus, additional in vitro models which include germ cells must come into use. In this Commentary, we hope to shed new light on how we may better study spermatocyte movement across the BTB

Indigenous sharing, collaboration and synchronous learning

Online learning is progressively accepted in Indigenous communities with the realized potential for sharing, collaboration and learning for adults living in remote and isolated communities. This study used a design-based research approach that provided opportunity to integrate the current literature, literacy practitioners\u27 views and community members\u27 self identified literacy needs to generate ten draft guiding principles which guided this study. A collaborative community engagement project was created by the community members in consideration of these principles and presented in three iterations in a synchronous environment which will lead to design-based principles for working with technology and Indigenous communities. This paper examines the framework and approach for this study, provides a short literature review and presents the draft guiding principles drawn from data collected from the stakeholders and from which the project was created

Порівняльна характеристика 3–4-річних самиць райдужної форелі, вирощених в умовах індустріального господарства «Слобода-Банилів»

Rational management of the trout economy requires the creation of high-quality productive uterine herds, which should maximally meet the requirements of farms in healthy life-sustaining landing material. However, numerous factors (high level of inbreeding, uncontrolled interbreeding of various tribal groups of fish, etc.) lead to a gradual decrease in reproductive parameters, degradation of breeding qualities and a decrease in the resistance of fish to diseases or adverse external factors of the environment. Therefore, the combination of research on phenotypic and productive features with genetic control at present is an advanced and necessary direction in domestic trout management. Selective-breeding works on the formation of rainbow trout brood stocks have been performed. It was found that the brood fish reared in the conditions of the industrial fish farm «Sloboda-Banyliv» despite instable rearing conditions were characterized by moderate growth rate and had high values of productive and reproductive features. The mean weight of age-3 rainbow trout females 1282.5 g. This parameter in age-4 fish was higher by 39.8%. Working fecundity of age-3 females 3.48 thousand eggs, in age-4 fish it was higher by 1.09 thousand eggs. Mean weights of eggs were 239.7 and 340.8 g, respectively; individual parameter of eggs increased with age by 6.7% in weight and by 1.9% by diameter.Раціональне ведення форелевого господарства потребує створення якісних продуктивних маточних стад, які повинні максимально задовольняти вимоги господарств у здоровому життєстійкому посадковому матеріалі. Разом з тим  численні фактори (високий рівень інбридингу, неконтрольоване схрещування різноманітних племінних груп риб тощо) призводять до поступового зменшення репродуктивних показників, погіршення племінних якостей та зниження резистентності риб до захворювань чи несприятливих зовнішніх чинників середовища. Тому поєднання досліджень фенотипових та продуктивних ознак з генетичним контролем  на теперішній час є передовим та необхідним  напрямом у вітчизняному форелівництві. Проведені селекційно-племінні роботи з формування маточних стад райдужної форелі. Виявлено, що плідники, вирощені в умовах індустріального господарства «Слобода-Банилів», попри нестабільні умови вирощування характеризувалися помірним темпом росту та мали високі значення як продуктивних, так і репродуктивних ознак. Середній показник маси самиць райдужної форелі у віці 3-х років складав 1282,5 г, у чотирирічному даний показник був вищим на 39,8%. Робоча плодючість трирічних самиць складала 3,48 тис. ікринок, у чотирирічних самиць вона була вищою на 1,09 тис. ікринок. Середні показники маси ікри становили  239,7 та 340,8 г відповідно; індивідуальні показники ікринок з віком зростали за масою на 6,7% та за діаметром – на 1,9%

Microtubule affinity-regulating kinase 4 (MARK4) is a component of the ectoplasmic specialization in the rat testis

During the seminiferous epithelial cycle of spermatogenesis, the ectoplasmic specialization (ES, a testis-specific adherens junction, AJ, type) maintains the polarity of elongating/elongated spermatids and confers adhesion to Sertoli cells in the seminiferous epithelium, and known as the apical ES. On the other hand, the ES is also found at the Sertoli-Sertoli cell interface at the blood-testis barrier (BTB) known as basal ES, which together with the tight junction (TJ), maintains Sertoli cell polarity and adhesion, creating a functional barrier that limits paracellular transport of substances across the BTB. However, the apical and basal ES are segregated and restricted to the adluminal compartment and the BTB, respectively. During the transit of preleptotene spermatocytes across the BTB and the release of sperm at spermiation at stage VIII of the seminiferous epithelial cycle, both the apical and basal ES undergo extensive restructuring to facilitate cell movement at these sites. The regulation of these events, in particular their coordination, remains unclear. Studies in other epithelia have shown that the tubulin cytoskeleton is intimately related to cell movement, and MARK [microtubule-associated protein (MAP)/microtubule affinity-regulating kinase] family kinases are crucial regulators of tubulin cytoskeleton stability. Herein MARK4, the predominant member of the MARK protein family in the testis, was shown to be expressed by both Sertoli and germ cells. MARK4 was also detected at the apical and basal ES, displaying highly restrictive spatiotemporal expression at these sites, as well as co-localizing with markers of the apical and basal ES. The expression of MARK4 was found to be stage-specific during the epithelial cycle, structurally associating with α-tubulin and the desmosomal adaptor plakophilin-2, but not with actin-based BTB proteins occludin, β-catenin and Eps8 (epidermal growth factor receptor pathway substrate 8, an actin bundling and barbed end capping protein). More importantly, it was shown that the expression of MARK4 tightly associated with the integrity of the apical ES because a diminished expression of MARK4 associated with apical ES disruption that led to the detachment of elongating/elongated spermatids from the epithelium. These findings thus illustrate that the integrity of apical ES, an actin-based and testis-specific AJ, is dependent not only on the actin filament network, but also on the tubulin-based cytoskeleton

N-WASP Is Required for Structural Integrity of the Blood-Testis Barrier

During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal (apical) and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation

Failure behavior of internally pressurized flawed and unflawed steam generator tubing at high temperatures -- Experiments and comparison with model predictions

This report summarizes experimental work performed at Argonne National Laboratory on the failure of internally pressurized steam generator tubing at high temperatures ({le} 700 C). A model was developed for predicting failure of flawed and unflawed steam generator tubes under internal pressure and temperature histories postulated to occur during severe accidents. The model was validated by failure tests on specimens with part-through-wall axial and circumferential flaws of various lengths and depths, conducted under various constant and ramped internal pressure and temperature conditions. The failure temperatures predicted by the model for two temperature and pressure histories, calculated for severe accidents initiated by a station blackout, agree very well with tests performed on both flawed and unflawed specimens