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Estimating Re and overdispersion in secondary cases from the size of identical sequence clusters of SARS-CoV-2.

The wealth of genomic data that was generated during the COVID-19 pandemic provides an exceptional opportunity to obtain information on the transmission of SARS-CoV-2. Specifically, there is great interest to better understand how the effective reproduction number [Formula: see text] and the overdispersion of secondary cases, which can be quantified by the negative binomial dispersion parameter k, changed over time and across regions and viral variants. The aim of our study was to develop a Bayesian framework to infer [Formula: see text] and k from viral sequence data. First, we developed a mathematical model for the distribution of the size of identical sequence clusters, in which we integrated viral transmission, the mutation rate of the virus, and incomplete case-detection. Second, we implemented this model within a Bayesian inference framework, allowing the estimation of [Formula: see text] and k from genomic data only. We validated this model in a simulation study. Third, we identified clusters of identical sequences in all SARS-CoV-2 sequences in 2021 from Switzerland, Denmark, and Germany that were available on GISAID. We obtained monthly estimates of the posterior distribution of [Formula: see text] and k, with the resulting [Formula: see text] estimates slightly lower than estimates obtained by other methods, and k comparable with previous results. We found comparatively higher estimates of k in Denmark which suggests less opportunities for superspreading and more controlled transmission compared to the other countries in 2021. Our model included an estimation of the case detection and sampling probability, but the estimates obtained had large uncertainty, reflecting the difficulty of estimating these parameters simultaneously. Our study presents a novel method to infer information on the transmission of infectious diseases and its heterogeneity using genomic data. With increasing availability of sequences of pathogens in the future, we expect that our method has the potential to provide new insights into the transmission and the overdispersion in secondary cases of other pathogens.

COVID-19

Diabetes mellitus in the guinea pig.

Spontaneous diabetes mellitus has been documented in a colony of guinea pigs. The contagious nature of the disease has been verified, but the nature of the infectious agent is not known. Animals from the original colony or animals exposed to the colony with normal glucose tolerance tests (GTT) became diabetic, as evidenced by elevated one- and four-hour GTT values, and in most cases have significant glycosuria. The severity of pathologic changes in the pancreatic islets parallel, in general, the severity of the clinical symptoms (glycosuria and abnormal GTT). Those animals with severe glycosuria and elevated FBS as well as one- and four-hour GTT values had the most pronounced degranulation and most prominent cytoplasmic inclusions in islet B cells. The severity of scarring in the islets can be correlated with the duration of the overt diabetic state. The other clinical parameters of note were elevated serum triglycerides, normal serum but elevated aortic cholesterol, and absence of ketonemia or ketonuria. The reproductive capacity of diabetic females was compromised. While the clinical manifestations are mild or variable, the presence of significant islet pathology is reminiscent of human juvenile diabetes mellitus. These findings lend support to the concept that infectious and/or immune mechanisms could be operative in the etiology and pathogenesis of human diabetes mellitus.

Animals

Haematological studies in relation to environmental temperature and different periods of breeding cycle in an air breathing fish, Heteropneustes fossilis.

Investigations were made on different haematological parameters in H. fossilis at two environmental temperature (18 degrees C and 32.5 degrees C) and different periods of breeding cycles. The RBC counts 302.0-10(4)/mm3), WBC counts (10.6-10(4)/mm3), Hb concentration (19.0g%), haematocrit (36.0%), M.C.H.C. (57.7%), total blood volumes (0.966 ml) and per cent blood volumes (1.542%) gave significantly high values but M.C.V. (119.2 micrometer3) and erythrocyte surfaces (52.96 micrometer2) gave low values at higher temperature (32.5 +/- 1 degrees C) and during breeding period (G.S.I. = 10.4 +/- 0.52 g). The higher values obtained for different haematological parameters during breeding period at high temperature may be probably related to greater physical activity and higher metabolic activity at the time of reproduction.

Animals

The production of migration inhibitory factor and reproductive capacity in allogeneic pregnancies.

Migration inhibitory factor (MIF) is produced during allogeneic pregnancies but not during syngeneic pregnancies. Removal of the paraaortic or paraaortic and renal lymph nodes significantly decreased MIF production whereas splenectomy did not. Removal of these regional lymph nodes decreased the mean litter size and increased the variance in the weights of the offspring, with the greatest changes occurring when both the paraaortic and renal lymph nodes were removed; splenectomy did not alter either parameter. None of the surgical procedures affected the gestation period significantly, but removal of the paraaortic and renal lymph nodes greatly reduced the rate of conception and increased the incidence of stillbirths. These findings support the proposition that a vigorous immune response occurs during allogeneic pregnancies and that this response provides reproductive advantages to the offspring.

Animals

Tdrd15 is dispensable for male fertility and spermatogenesis in the golden hamster.

Tudor domain-containing proteins (TDRDs) constitute an evolutionarily conserved protein family and are critical for germline development and piRNA pathway regulation, with established roles in male fertility. While multiple TDRD family members have been functionally linked to spermatogenic impairment, the precise biological role of TDRD15 remains to be elucidated. We used CRISPR/Cas9-mediated gene editing to generate Tdrd15 knockout (KO) golden hamsters (Mesocricetus auratus), a model necessitated by the absence of a functional Tdrd15 ortholog in the mouse genome, to investigate its function in male reproduction. Phylogenetic analysis demonstrated that TDRD15 is strongly conserved among eutherian mammals, with testis-restricted expression patterns in hamsters. Despite the successful induction of frameshift mutations and significant transcriptional knockdown, Tdrd15 KO males maintained normal fertility parameters, including unaltered testicular architecture, spermatogenic progression (confirmed by periodic acidic-Schiff (PAS) staining and immunohistochemistry), and sperm quality metrics determined using a computer-assisted analysis. Quantitative polymerase chain reaction (qPCR) revealed compensatory overexpression of paralogous Tdrd genes in KO testes, implying functional redundancy within this protein family. This study provides the first experimental evidence that TDRD15 is dispensable for male fertility in golden hamsters under physiological conditions, thereby challenging the prevailing assumptions of its obligatory function in spermiogenesis. Altogether, these findings support a more targeted allocation of research efforts within the field of male reproductive biology.

Animals

Initiation of hamster sperm motility from quiescence: effect of conditions upon flagellation and respiration.

The point within the male reproductive tract where sperm motility originates varies with mammalian species. Premotile sperm from hamster, a species whose sperm are still quiescent in the epididymis, were used here to investigate further the parameters involved in the initiation of sperm motility. Two types of motility were produced: (1) partial, weak flagellation by simple dilution; (2) strong, complete motility by inducers (calcium, cyclic adenosine 3':5'-monophosphate) in the presence of amplifiers (caffeine, spermine). Expansion of initiation conditions to test tube volumes revealed that, at high sperm dilutions, bicarbonate could also induce motility. The respiratory consequences of sperm motility induction were measured. A Large, short-term burst of oxygen consumption occurred at a time paralleling the previously reported shifts in nucleotide levels associated with this event.

Animals

The evolution of sexual reproduction as a repair mechanism. Part I. A model for self-repair and its biological implications.

The theory is presented that the sexual process is a repair mechanism which maintains redundancy within the sub-structure of hierarchical, self-reproducing organisms. In order to keep the problems within mathematically tractable limits (see Part II), a simple model is introduced: a wheel with 6 spokes, 3 of them vital and 3 redundant, symbolizes the individual (cell or organism). Random accidents destroy spokes; the wheels replicate at regular cycles and engage periodically in pairing and repair phases during which missing spokes are copy-reproduced along the intact spokes of the partner wheel. The hierarchical structure of such a system is analysed and an 'autonomous unit' is defined: this is the unit of minimal hierarchical complexity which is capable of perpetuating autonomously all higher and all lower levels of the hierarchy; this is the central unit of selection. Four basic, physical parameters are isolated which determine the essential features of any eucaryotic life cycle: 1. The number of levels of the hierarchy (unicellular, multicellular, colonial, etc.); 2. the relation between the phases of replication (asexual generations) and repair (sexual generations); 3. the duration of potential repair (haplo-diplo-phase); 4. the position of the sexual partners within the hierarchy (selfing, monecy, dioecy, reproductive individuals within colonies, etc.). The evaluation of fitness components is considered in relation to trends of reproductive patterns in evolution.

Animals

Effect of cyproterone acetate on the genital organs of female rats.

Effects of cyproterone acetate, a synthetic steroidal compound, on the reproductive organs of female rats have been investigated. This agent causes reduction in ovarian weights indicative of suppression of pituitary gonadotrophins. Oestrogenic nature of cyproterone acetate was investigated in intact and ovariectomized animals taking uterine weight, vaginal keratinization and other oestrogen sensitive biochemical parameters. Cyproterone acetate in ovariectomized animals induced vaginal keratinization, increase in uterine weight and uterine protein, RNA, glycogen and sialic acid contents. These effects were parallel to the effect of oestradiol dipropionate in ovariectomized animals, thus indicating oestrogenic activity cyproterone acetate. The histological and biochemical parameters lead to the conclusion that cyproterone acetate possessed antifertility property due to its inherent oestrogenic nature.

Adrenal Glands

Scion-based drought stress memory affects potato response to water deficit.

A scion-based stress memory signal, which was derived from drought-primed potato plants, was transmitted to new potato plants generated through vegetative reproduction. This affected potato tuber yield. Drought is one of the most significant threats to agricultural productivity worldwide. The cultivated potato (Solanum tuberosum L.) is a crop species that is sensitive to drought stress. This study investigated the impact of scion-based drought stress memory on tuber yield, physiological parameters, gene expression, and DNA methylation in the vegetative progeny of grafted plants. The tuber progeny plants remembered the drought stress signal transmitted from the drought-primed scion. Significant changes were observed in the expression of genes, primarily those related to photosynthetic metabolic pathways, as well as those associated with chromatin remodeling, DNA repair, and the plant's response to abiotic stresses. The gene expression landscape corresponded with variability in chlorophyll fluorescence parameters. In the first and the second generation of vegetatively propagated plants, scion-based memory had a positive effect on tuber yield. This was achieved by buffering the decline in yield caused by drought, as compared to plants grown under control conditions. Whole-genome bisulfite sequencing analysis revealed no correlation between changes in DNA methylation and gene expression. Drought-induced alterations in DNA methylation were erased in the second progeny generation. We propose that there is a direct causal relationship between scion-based memory of drought stress and photosynthetic efficiency, as well as potato tuber productivity.

Solanum tuberosum

Multimodal Therapy With Metformin, Inositol and Dietary Restriction Improves Insulin Resistance and Endocrine Outcomes in Women With Polyendocrine Metabolic Ovarian Syndrome: A Randomized Controlled Trial.

INTRODUCTION: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine-metabolic disorder characterized by insulin resistance, hyperandrogenism and ovulatory dysfunction. Metformin, inositol supplementation and lifestyle modification are widely used treatments, but direct comparative evidence remains limited. Multimodal therapy combining metformin, inositol and dietary restriction produces greater metabolic and reproductive improvement than single-modality interventions. METHODS: We conducted a 12-week randomized controlled trial in 192 women aged 18-35 years diagnosed with PMOS according to Rotterdam criteria. Participants were allocated to metformin (1500-2000 mg/day), inositol (myo-inositol 2&#x2009;g plus d-chiro-inositol 50&#x2009;mg twice daily), calorie-restricted diet (1200-1500&#x2009;kcal/day), or combination therapy. Primary outcomes included changes in body mass index (BMI) and insulin resistance assessed by HOMA-IR. Secondary outcomes included testosterone, LH/FSH ratio and menstrual regularity. Analysis was performed using analysis of covariance (ANCOVA), with post-intervention values as dependent variables and corresponding baseline values as covariates. Categorical outcomes were compared using the Chi-square test. RESULTS: All interventions improved metabolic and endocrine parameters. Combination therapy resulted in the greatest reduction in HOMA-IR (-&#x2009;2.64, 95% CI&#x2009;-&#x2009;2.82 to -2.46, p&#x2009;<&#x2009;0.001) and BMI (-&#x2009;2.8&#x2009;kg/m2, 95% CI&#x2009;-&#x2009;3.05 to -2.55, p&#x2009;<&#x2009;0.001). Menstrual cyclicity improved across all groups, with the highest proportion of participants reporting cycle regularisation in the combination therapy group (85.4%), compared with dietary restriction (72.9%), inositol (64.6%), and metformin (39.6%) (p&#x2009;<&#x2009;0.001). Given the short follow-up duration, these findings reflect early improvements rather than sustained normalisation. CONCLUSION: Multimodal therapy was associated with superior metabolic and reproductive outcomes compared with single-modality interventions in women with PMOS. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov (NCT07380841).

Humans

Morphology, histochemistry and biochemistry of the oviduct of the toad, Bufo vulgaris (Anura, Amphibia), during the annual reproductive cycle.

On the basis of histological and histochemical characteristics the oviduct of adult Bufo vulgaris can be separated into six zones. These characteristics include mainly the relative abundance of secretory and ciliated epithelial cells, mucosal foldings, tubular glands and the staining properties of the secretory elements. The VI zone (uterine segment) is totally deprived of tubular glands and is profoundly rich in epithelial secretory cells. These cells and the tubular glands, when well-developed, are rich in neutral and acid mucins in the preovulatory phase, whereas this content is greatly diminished after ovulation. Similarly, the weight and the length of the oviduct displays a marked seasonal pattern. The same is observed for its protein content and acid and alkaline phosphatases. These parameters show the highest values in the preovulatory period and lowest after ovulation. The toad oviduct also displays marked hydroxysteroid dehydrogenase activity along the mucosal epithelium. Its functional significance remains a matter of debate, however. A marked parallelism between the present data and those obtained by others in other amphibians indicates the existence of a common pattern of seasonal modifications correlated mainly with the release of the eggs and the formation of their multi-layered coat.

Acid Phosphatase

[Reproducibility of measurements of arterial pressure and heart rate during exercise test: its significance and application].

The authors report their findings from a study of the reproductibility of measurements of blood pressure and heart rate both at rest and during exercise (work on a bicycle ergometer) in 19 patients who were tested on two occasions with a mean interval of 9.8 days. A study of the correlations, of variability, and of the findings on applying Student's "t" test, have led us to the conclusion that these parameters are more reproduceable on exercise than at rest, and become increasingly reproduceable as exercise increases. These conclusions support the use of an induced hypertension test under exercise.

Adult

Spermidine and melatonin ameliorate heat stress-induced decline in sheep semen quality.

Heat stress impairs reproductive performance in sheep through endocrine disruption and oxidative stress. This study evaluated the protective effects of spermidine (SPD) and melatonin (MT) supplementation on semen quality in Dorper rams during summer. Twenty-four rams were randomly assigned to a control group, an SPD group (5&#x202f;mg/kg, dietary supplementation), or an MT group (60&#x202f;mg, subcutaneous implantation) and treated for 60 days. The temperature-humidity index (THI) was monitored throughout the experimental period. Compared with the control group, MT significantly reduced serum cortisol concentration on day 30 (P&#x202f;<&#x202f;0.05), whereas no significant differences were observed at the other sampling time points. Serum testosterone, spermidine, and melatonin concentrations remained unchanged throughout the study (P&#x202f;>&#x202f;0.05). SPD supplementation significantly increased ejaculate volume on day 35 and sperm motility on day 42 (P&#x202f;<&#x202f;0.05), whereas MT did not significantly affect these parameters. Neither treatment reduced the overall sperm abnormality rate. However, both SPD and MT significantly decreased the proportion of acephalic and decaudated sperm on day 56 (P&#x202f;<&#x202f;0.05). Neither treatment significantly affected pregnancy rate, delivery rate, or the expression of PMFBP1 and SUN5 proteins in semen (P&#x202f;>&#x202f;0.05). Regarding oxidative stress, MT significantly downregulated CAT protein expression (P&#x202f;<&#x202f;0.05), whereas SPD significantly reduced MDA content and SOD1 protein expression (P&#x202f;<&#x202f;0.05); MT showed similar but non-significant trends for these two markers (P&#x202f;>&#x202f;0.05). Collectively, these findings demonstrate that SPD and MT exert distinct protective effects against heat stress, with SPD improving selected semen quality traits and both treatments reducing sperm head-tail separation, although these benefits did not translate into improved reproductive performance.

Animals

The value of the basal temperature chart in the management of infertility.

The basal temperature chart (BTC) has been used as a means of screening the ovarian function of infertile patients and for monitoring their response to ovarian stimulation. During three years in a busy infertility clinic, specifically designated for cases of functional infertility, 491 patients were seen and 96 per cent of them kept valid basal temperature charts. The use of the BTC enabled therapy to be instituted early on in the course of investigations in those cases of infertility in which there was an endocrine factor. There were 420 patients in this category; of those who received treatment a high percentage became pregnant in contrast to those who were being observed. It is recommended that the BTC should be used early and more frequently in the management of cases of infertility, since it has been shown to serve as an inexpensive and convenient parameter of ovarian function.

Anovulation

Quantitative parameters for light microscopic assessment of the tubuli seminiferi.

For quantitative, histologic assessment of the testis tubuli there are four suitable parameters: diameter of tubulus, area of tubulus, number of cell nuclei per tubulus, and area of nuclei of the various cells participating in spermatogenesis. For estimating areas, the integrative method of measurement, either with a grid or with the aid of the manual optical picture-analysis system, is proposed. The tubulus diameter can be determined rapidly and easily, although the tubulus size can be assessed more accurately by area estimation. An assessment of reproductive capacity in detail is possible by means of rather time-consuming determination of cell nucleus number and nuclear area, whereby the stages of the cycle of the seminiferous epithelium must be considered.

Age Factors

Circannual and circadian rhythms in the concentration of corticosterone in the plasma of the edible frog (Rana esculenta L.).

For a period of 21 months between May 1974 and September 1976, circadian variations in the plasma concentration of corticosterone were studied by competitive protein-binding techniques in mature male and female edible frogs living in their natural environment. Blood samples were taken from 8 to 12 frogs six times daily and conventional and cosinor methods were used for statistical analysis. Circadian rhythms were not detected during February and March (time of hibernation). Circannual rhythms were detected in three parameters of the circadian rhythm. The mean concentration of corticosterone over a 24 h period (24 h mean) reached a peak on 1 May (between 15 April and 15 May; 95% limits of confidence); the annual mean value of the 24 h means was 1.97 +/- 0.25 (S.E.M.) microgram/100 ml, with an amplitude of 0.66 microgram/100 ml (0.53--0.79 microgram/100 ml; 95% limits of confidence). Circadian variations in the concentration of corticosterone were largest in May (peak of reproductive activity). The times at which the peak concentration of corticosterone occurred showed circannual variations: peak values were detected around 24.00 h in May, 19.00 h in July and 08.00 h in November. Both circadian and circannual variations have therefore been demonstrated in an endocrine function of an amphibian in its natural habitat.

Animals

The value of urinary steroid analysis in chorionic neoplasia.

The profile of urinary neutral steroids was investigated in normal pregnancy and chorionic neoplasia by gas-liquid chromatography. The whole chramatogram was divided into three metabolically distinct fractions. The excretion of fraction 2, including four menstruation-dependent steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetrial), was remarkably increased in normal pregnancy as compared with that in nonpregnant controls. But the same parameter was differentially reduced in hydatidiform mole (HM) and chorioadenoma destruens (CA) as compared with normal pregnancy, and the ratio of fraction 2 to fraction 1 (11-deoxy-17-ketosteroids) was found useful in separating normal pregnancy, HM, and CA from each other. In choriocarcinoma (CC), reduced excretion was observed in both fraction 1 and fraction 2 steroids. The linear relationship between the logarithm of fraction 2-fraction 1 ratio and that of pregnanediol excretion, as observed in the reproductive cycle of a healthy woman, was not detectable in women with CA, whose urine revealed a low value of log (fraction 2/fraction 1) in spite of an abundant HCG content. It is indicated that the above findings reflect the deficiency of ovarian steroidogenesis under the influence of abnormal HCG from tumors.

Adrenal Cortex Hormones

Veterinary aspects of salmonid fish farming: husbandry.

A knowledge of environmental requirements is important in order to obtain good growth and health when farming salmonid fish. Biological requirements are discussed, including water quality parameters and nutritional aspects. The main techniques used for farming salmonids are described together with the annual cycle of operations undertaken on a commercial trout farm.

Ammonia