Structure and behaviour of the sperm terminal filament

Light- and electron-microscopic observations of Ciona and Lytechinus spermatozoa show a thin terminal filament at the distal end. The terminal filament is 5-6 microns long and contains the two central microtubules and a variable number of A-tubule extensions of the peripheral doublet microtubules. The transition from the 9 + 2 region to the terminal filament is tapered more gradually in Lytechinus than in Ciona. Photographs of the movement of beating spermatozoa do not show any obvious discontinuity in curvature at the transition region. Bends are propagated smoothly off the end of the flagellum with no decrease in curvature. However, spermatozoa in which the terminal filament has been removed show a clear 'end effect'. This end effect involves a rapid unbending of bends that have reached the distal end of the flagellum. Computer simulations of flagellar models lacking a terminal filament show a similar end effect. Addition of a terminal filament to the end of the computer model can eliminate the end effect. Realistic bending behaviour of the model is obtained by using a terminal filament with a tapered elastic bending resistance in the basal portion of the terminal filament and a value of 0.03 x 10^(9) pN nm^2 in the remainder of the terminal filament. This leads to estimates of 0.01 x 10^(9) pN nm^2 for the elastic bending resistance of an individual microtubule, and 0.2 x 10^(9) pN nm^2 for the elastic bending resistance of the 9 + 2 region of the flagellum. An improvement in propulsive effectiveness by addition of a terminal filament remains to be demonstrated

The optimal elastic flagellum

Motile eukaryotic cells propel themselves in viscous fluids by passing waves of bending deformation down their flagella. An infinitely long flagellum achieves a hydrodynamically optimal low-Reynolds number locomotion when the angle between its local tangent and the swimming direction remains constant along its length. Optimal flagella therefore adopt the shape of a helix in three dimensions (smooth) and that of a sawtooth in two dimensions (non-smooth). Physically, biological organisms (or engineered micro-swimmers) must expend internal energy in order to produce the waves of deformation responsible for the motion. Here we propose a physically-motivated derivation of the optimal flagellum shape. We determine analytically and numerically the shape of the flagellar wave which leads to the fastest swimming while minimizing an appropriately-defined energetic expenditure. Our novel approach is to define an energy which includes not only the work against the surrounding fluid, but also (1) the energy stored elastically in the bending of the flagellum, (2) the energy stored elastically in the internal sliding of the polymeric filaments which are responsible for the generation of the bending waves (microtubules), and (3) the viscous dissipation due to the presence of an internal fluid. This approach regularizes the optimal sawtooth shape for two-dimensional deformation at the expense of a small loss in hydrodynamic efficiency. The optimal waveforms of finite-size flagella are shown to depend upon a competition between rotational motions and bending costs, and we observe a surprising bias towards half-integer wave-numbers. Their final hydrodynamic efficiencies are above 6%, significantly larger than those of swimming cells, therefore indicating available room for further biological tuning

The frequency in Japanese of genetic variants of 22 proteins III. Phosphoglucomutase-1, phosphoglucomutase-2, 6-phosphogluconate dehydrogenase, adenylate kinase, and adenosine deaminase

Five enzyme systems, PGM 1 , PGM 2 , ADA, 6-PGD and AK, were examined by electrophoresis in over 4000 samples from Hiroshima and Nagasaki for the frequencies of common and rare variants. In the PGM 1 , system, the PGM 2 1 allele and PGM 7 1 ; allele were found in polymorphic proportions. I n addition, five kinds of slow variants and three types of fast variants of PGM 1 were detected. The PGM 3 NGS 1 1 allele was found in five individuals from Nagasaki, but was not observed in samples from Hiroshima. There were no variants of PGM 2 . Three kinds of fast variants of 6-PGD were detected. NO variation in AK was observed. There were no rare variants of ADA. The 6-PGD c allele had a frequency of 0.084 in Hiroshima, and 0.093 in Nagasaki, and the ADA 2 allele frequencies of 0.025 in Hiroshima and 0.032 in Nagasaki.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65524/1/j.1469-1809.1977.tb01912.x.pd

“There is nothing that can prevent me from supporting her:” men’s perspectives on their involvement and support of women’s use of topical therapy for cervical precancer treatment in Kenya

Purpose: Cervical cancer disproportionately impacts women in low- and middle-income countries (LMICs). The World Health Organization’s (WHO) 90/70/90 strategy aims to eliminate cervical cancer by 2030 by increasing HPV vaccination coverage to 90%, screening 70% of eligible women, and effectively treating 90% of those with abnormal results by 2030, potentially preventing 62 million deaths in LMICs. LMICs, however, struggle with limited access to cervical precancer treatment, in part due to a lack of trained professionals and weak health systems. Effective non-surgical, self-administered, which have demonstrated efficacy in high-income countries, could bridge the treatment gap in LMICs and may be more scalable and cost-effective than provider-administered therapies. To inform feasibility studies in LMICs, data are needed on the role of male partners in influencing the acceptability and uptake of self-administered topical therapies, including their support of recommended abstinence and contraception guidelines associated with these therapies. Methods: Between November 2022 and April 2023, we conducted five focus group discussions (FGDs) with men aged 25 to 65 years in Kenya to explore their perspective and perceived support regarding their female partners using topical self-administered therapies for cervical precancer treatment. The FGDs were moderated by local qualitative research assistants and conducted in local languages, transcribed, coded, and analyzed using qualitative description. Results: Thirty-nine male participants meeting the eligibility criteria participated in five FGDs. The mean age of participants was 42.5 years. Most participants, 79.5%, had a female partner with a history of cervical precancer treatment, 5.1% did not, and 15.4% were unsure of their female partner’s prior precancer treatment history. The study aimed to assess men’s support of their female partners’ use of topical therapies for treating cervical precancer. We find that male participants strongly express acceptance and willingness to support their wives or partners in using such therapies, if available. Reported supportive behavior included permitting the use of the therapies and support of maintaining abstinence during the recommended times. Additionally, participants desired male involvement in clinic and community-based education about topical therapies to facilitate widespread support. Conclusion: The use of self-administered topical therapies for cervical precancer treatment, if supported by efficacy studies in LMICs, may support achieving the WHO’s 2030 goal of 90% treatment access. We find that with adequate education, men express overwhelming support of their female partner’s use of topical therapies, including adherence to abstinence and contraception guidelines

Modulation of gene-specific epigenetic states and transcription by non-coding RNAs

Emerging evidence points to a role for long non-coding RNAs in the modulation of epigenetic states and transcription in human cells. New insights, using various forms of small non-coding RNAs, suggest that a mechanism of action is operative in human cells, which utilizes non-coding RNAs to direct epigenetic marks to homology containing loci resulting ultimately in the epigenetic-based modulation of gene transcription. Importantly, insights into this mechanism of action have allowed for certain target sequences, which are either actively involved in RNA mediated epigenetic regulation or targets for non-coding RNA based epigenetic regulation, to be selected. As such, it is now feasible to utilize small antisense RNAs to either epigenetically silence a gene expression or remove epigenetic silencing of endogenous non-coding RNAs and essentially turn on a gene expression. Knowledge of this emerging RNA-based epigenetic regulatory network and our ability to cognitively control gene expression has deep implications in the development of an entirely new area of pharmacopeia

Genetic heterogeneity within an electrophoretic phenotype of phosphoglucose isomerase in a Japanese population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65884/1/j.1469-1809.1979.tb00662.x.pd

Anthropology and GIS: Temporal and Spatial Distribution of the Philippine Negrito Groups

The Philippine negrito groups comprise a diverse group of populations speaking over 30 different languages, who are spread all over the archipelago, mostly in marginal areas of Luzon Island in the north, the central Visayas islands, and Mindanao in the south. They exhibit physical characteristics that are different from more than 100 Philippine ethnolinguistic groups that are categorized as non-negritos. Given their numbers, it is not surprising that Philippine negritos make up a major category in a number of general ethnographic maps produced since the nineteenth century. Reports from various ethnological surveys during this period, however, have further enriched our understanding regarding the extent and distribution of negrito populations. Using the data contained in these reports, it is possible to plot and create a map showing the historical locations and distribution of negrito groups. Using geographic information systems (GIS), the location and distribution of negrito groups at any given time can be overlaid on historical or current maps. In the present study, a GIS layer was compiled and extracted from the 2000 Philippine Census of population at the village level and overlaid on existing maps of the Philippines. The maps that were generated from this project will complement ongoing anthropological and genetic studies of negrito groups that inhabit different locations within the Philippine archipelago

Interfering RNA and HIV: Reciprocal Interferences

In this review, a quick presentation of what interfering RNA (iRNA) are—small RNA able to exert an inhibition on gene expression at a posttranscriptional level, based on sequence homology between the iRNA and the mRNA—will be given. The many faces of the interrelations between iRNA and viruses, particularly HIV, will be reviewed. Four kinds of interactions have been described: i) iRNA of viral origin blocking viral RNA, ii) iRNA of viral origin downregulating cellular mRNA, iii) iRNA of cellular origin (microRNA) targeting viral RNA, and iv) microRNA downregulating cellular mRNA encoding cell proteins used by the virus for its replication. Next, HIV strategies to manipulate these interrelations will be considered: suppression of iRNA biosynthesis by Tat, trapping by the HIV TAR sequence of a cell component, TRBP, necessary for iRNA production and action, and induction by the virus of some microRNA together with suppression of others. Then, we will discuss the putative effects of these mutual influences on viral replication as well as on viral latency, immune response, and viral cytopathogenicity. Finally, the potential consequences on the human infection of genetic polymorphisms in microRNA genes and the therapeutic potential of iRNA will be presented

The hydrocephalus inducing gene product, Hydin, positions axonemal central pair microtubules

<p>Abstract</p> <p>Background</p> <p>Impairment of cilia and flagella function underlies a growing number of human genetic diseases. Mutations in <it>hydin </it>in <it>hy3 </it>mice cause lethal communicating hydrocephalus with early onset. Hydin was recently identified as an axonemal protein; however, its function is as yet unknown.</p> <p>Results</p> <p>Here we use RNAi in <it>Trypanosoma brucei </it>to address this issue and demonstrate that loss of Hydin causes slow growth and a loss of cell motility. We show that two separate defects in newly-formed flagellar central pair microtubules underlie the loss of cell motility. At early time-points after RNAi induction, the central pair becomes mispositioned, while at later time points the central pair is lost. While the basal body is unaffected, both defects originate at the basal plate, reflecting a role for TbHydin throughout the length of the central pair.</p> <p>Conclusion</p> <p>Our data provide the first evidence of Hydin's role within the trypanosome axoneme, and reveal central pair anomalies and thus impairment of ependymal ciliary motility as the likely cause of the hydrocephalus observed in the <it>hy3 </it>mouse.</p