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Disruption of meiosis and DNA repair genes is associated with female fertility disorders like premature ovarian insufficiency (POI). In this study, we identified a homozygous missense variant in the HELQ gene (c.596 A>C; p.Gln199Pro) through whole exome sequencing in a POI patient, a condition associated with disrupted ovarian function and female infertility. HELQ, an enzyme involved in DNA repair, plays a crucial role in repairing DNA cross-links and has been linked to germ cell maintenance, fertility, and tumour suppression in mice. To explore the potential association of the HELQ variant with POI, we used CRISPR/Cas9 to create a knock-in mouse model harbouring the equivalent of the human HELQ variant identified in the POI patient. Surprisingly, Helq knock-in mice showed no discernible phenotype, with fertility levels, histological features, and follicle development similar to wild-type mice. Despite the lack of observable effects in mice, the potential role of HELQ in human fertility, especially in the context of POI, should not be dismissed. Larger studies encompassing diverse ethnic populations and alternative functional approaches will be necessary to further examine the role of HELQ in POI. Our results underscore the potential uncertainties associated with genomic variants and the limitations of in vivo animal modelling. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is a common cause of infertility in women, characterised by amenorrhea and elevated FSH under the age of 40 years. In some cases, POI is syndromic in association with other features such as sensorineural hearing loss in Perrault syndrome. POI is a heterogeneous disease with over 80 causative genes known so far; however, these explain only a minority of cases. Using whole-exome sequencing (WES), we identified a MRPL50 homozygous missense variant (c.335T > A; p.Val112Asp) shared by twin sisters presenting with POI, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction. MRPL50 encodes a component of the large subunit of the mitochondrial ribosome. Using quantitative proteomics and western blot analysis on patient fibroblasts, we demonstrated a loss of MRPL50 protein and an associated destabilisation of the large subunit of the mitochondrial ribosome whilst the small subunit was preserved. The mitochondrial ribosome is responsible for the translation of subunits of the mitochondrial oxidative phosphorylation machinery, and we found patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. These data support a biochemical phenotype associated with MRPL50 variants. We validated the association of MRPL50 with the clinical phenotype by knockdown/knockout of mRpL50 in Drosophila, which resulted abnormal ovarian development. In conclusion, we have shown that a MRPL50 missense variant destabilises the mitochondrial ribosome, leading to oxidative phosphorylation deficiency and syndromic POI, highlighting the importance of mitochondrial support in ovarian development and function. [ABSTRACT FROM AUTHOR]

The Romanian Oltul Mijlociu-Cibin-Hârtibaciu Natura 2000 site of community importance (SCI) was designated for the purpose of protecting biodiversity and maintaining the wild flora and fauna in a favourable conservation status, as well as the natural habitats of conservation interest. This research focused on the possible disparition of one protected fish species Pelecus cultratus (Linnaeus, 1758) and the appearance of an alien one Babka gymnotrachelus (Kessler, 1857), as ecological indicators of the fact that at least this Natura 2000 site is far from being properly protected and a new, more responsible way should be followed and different administrators put in charge of the areas management. [ABSTRACT FROM AUTHOR]

Simple Summary: Fish are an important source of proteins of a high biological value, of some vitamins and minerals, and of polyunsaturated omega-3 fatty acids. However, fish products can also allow harmful substances, like heavy metals, to enter the diet. Such substances are recognized as being the most serious contaminants for aquatic ecosystems at the present time. Their non-biodegradability allows them to accumulate in fish tissues, and then pass into human diets. Therefore, our study aimed to determine the concentrations of heavy metals (As, Cd, Cu, Hg, Ni, Pb, and Zn), and to evaluate the bioaccumulation patterns in the different types of musculature in two species of fish of commercial interest, Chelon auratus and Chelon saliens, from the south coast of the Caspian Sea. The results obtained emphasize the need to continue to monitor and evaluate the degree of pollution in the sampled area, both in fish and other species and also in the environment, as well as recommending prevention measures orientated towards limiting and/or reducing the excessive exposure of the human population to heavy metal contamination. Although fish is a food that supplies nutrients of a high biological value, they can also be a source of some harmful substances, such as heavy metals. In the same context, some human activities in the Caspian Sea have contaminated this ecosystem during the past few years. For those reasons, our objective consisted of determining the concentrations of heavy metals and evaluating their bioaccumulation patterns in the different types of musculature in two species of mullets of commercial interest, Chelon auratus and Chelon saliens, from the southern coast of this sea. For this purpose, 20 C. auratus and 29 C. saliens were caught off this coastline and the metal concentrations in 3 different muscle locations were analyzed: the ventral, dorsal and caudal muscles of each fish. The caudal muscle had higher concentrations of Cd, Cu, Pb, and Zn, whereas As, Hg and Ni accumulation seemed to be independent of the musculature type. Overall, the Cd, Hg, and Pb concentrations exceeded the maximum levels permitted in fish by the European Union. In addition, the relationships between pairs of metals were positive and elevated in all the cases, which could be a sign of heavy metal pollution in the region sampled. Therefore, it will be necessary to continue monitoring and evaluating the degree of pollution in the Caspian Sea. [ABSTRACT FROM AUTHOR]

In this paper, we study the number of limit cycles for discontinuous piecewise differential systems formed by two differential systems separated by a straight line, when these differential systems are quadratic isochronous centers in a half-plane and the cubic isochronous centers in the other one. We deal with eight classes of discontinuous piecewise differential systems formed by these types of isochronous centers, and we provide an upper bound for the maximum number of limit cycles for these classes that can exhibit. Also, we show that the corresponding maximum number of limit cycles in four classes is reached. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is characterised by amenorrhea associated with elevated follicle stimulating hormone (FSH) under the age of 40 years and affects 1–3.7% women. Genetic factors explain 20–30% of POI cases, but most causes remain unknown despite genomic advancements. We used whole exome sequencing (WES) in four Iranian families, validated variants via Sanger sequencing, and conducted the Acyl-cLIP assay to measure HHAT enzyme activity. Despite ethnic homogeneity, WES revealed diverse genetic causes, including a novel homozygous nonsense variant in SYCP2L , impacting synaptonemal complex (SC) assembly, in the first family. Interestingly, the second family had two independent causes for amenorrhea – the mother had POI due to a novel homozygous loss-of-function variant in FANCM (required for chromosomal stability) and her daughter had primary amenorrhea due to a novel homozygous GNRHR (required for gonadotropic signalling) frameshift variant. WES analysis also provided cytogenetic insights. WES revealed one individual was in fact 46, XY and had a novel homozygous missense variant of uncertain significance in HHAT , potentially responsible for complete sex reversal although functional assays did not support impaired HHAT activity. In the remaining individual, WES indicated likely mosaic Turners with the majority of X chromosome variants having an allelic balance of ∼85% or ∼15%. Microarray validated the individual had 90% 45,XO. This study demonstrates the diverse causes of amenorrhea in a small, isolated ethnic cohort highlighting how a genetic cause in one individual may not clarify familial cases. We propose that, in time, genomic sequencing may become a single universal test required for the diagnosis of infertility conditions such as POI. • Discovery of diverse causes of amenorrhea in an ethnically restricted cohort. • Expansion of the genotypic spectrum associated with amenorrhea. • Novel causal variants in SYCP2L, FANCM and GNRHR. • Importance of functional validation before assigning variant pathogenicity. • Potential of exome sequencing as a first-line diagnostic test for amenorrhea. [ABSTRACT FROM AUTHOR]

The aims and objectives of the current study are to investigate the vibration analysis of the graphene sheet with attached spring, mass, and damper system for the first time. For this purpose, the governing equation is derived employing Hamilton's principle regarding the nonlocal Eringen theory. The graphene sheet is supposed to be rested on a Winkler elastic foundation. Galerkin's method is being used to obtain frequency on various boundary conditions. To validate our work, the proposed model is demonstrated by comprising the present model with the results available in the literature. The influence of different parameters such as the attached mass, nonlocal parameter, aspect ratio, and Winkler foundation of a graphene sheet on the non-dimensional vibration frequencies are presented in detail. The results indicate that adding the spring-mass system leads to an increase in the non-dimensional frequency parameter. The outcomes of this survey can be utilized in the construction of biological and chemical nanosensors. [ABSTRACT FROM AUTHOR]

Demographic data of the great sturgeon, Huso huso, from the Iranian coastal waters of the Caspian Sea were derived from measurements of individuals with a fork length ranging from 84 to 255 cm, obtained from commercial fisheries. The maximum age of fish caught in the south Caspian Sea was 30 years. The estimates of the asymptotic length L∞ and the growth coefficient (K) were 265.255 cm and 0.062 per year for males and 275.78 cm and 0.08 per year for females, respectively. Total mortality rates obtained by Gulland's method were larger for males (0.64) than for females (0.46). Annual mortality rates were calculated as 47% for males and 37% for females. Data obtained in this study and their comparison with data from previous studies indicate that the great sturgeon stock is definitely exploited in an unsustainable manner. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is a disorder characterized by oligomenorrhea, anovulation, and hyperandrogenism. Altered mitochondrial biogenesis can result in hyperandrogenism. The goal of this study was to examine the effect of vitamin D3 on mitochondrial biogenesis of the granulosa cells in the PCOS‐induced mouse model. Vitamin D3 applies its effect via the mitogen‐activated pathway kinase‐extracellular signal‐regulated kinases (MAPK‐ERK1/2) pathway. The PCOS mouse model was induced by the injection of dehydroepiandrosterone (DHEA). Isolated granulosa cells were subsequently treated with vitamin D3, MAPK activator, and MAPK inhibitor. Gene expression levels were measured using real‐time polymerase chain reaction. MAPK proteins were investigated by western blot analysis. We also determined reactive oxygen species (ROS) levels with 2′, 7′‐dichlorofluorescein diacetate. Mitochondrial membrane potential (mtMP) was also measured by TMJC1. Mitochondrial biogenesis (peroxisome proliferator‐activated receptor gamma coactivator 1‐α and nuclear respiratory factor), antioxidant (superoxide dismutase, glutathione peroxidase, and catalase), and antiapoptotic (B‐cell lymphoma‐2) genes were upregulated in the PCOS mice that treated with vitamin D3 compared with the PCOS mice without any treatment. Vitamin D3 and MAPK activator‐treated groups also reduced ROS levels compared with the nontreated PCOS group. In summary, vitamin D3 and MAPK activator increased the levels of mitochondrial biogenesis, MAPK pathway, and mtMP markers, while concomitantly decreased ROS levels in granulosa cells of the PCOS‐induced mice. This study suggests that vitamin D3 may improve mitochondrial biogenesis through stimulation of the MAPK pathway in cultured granulosa cells of DHEA‐induced PCOS mice which yet to be investigated. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder diagnosed by anovulation hyperandrogenism. Hyperandrogenism increases apoptosis, which will eventually disturb follicular growth in PCOS patients. Since mitochondria regulate apoptosis, they might be affected by high incidence of follicular atresia. This may cause infertility. Since vitamin D3 has been shown to improve the PCOS symptoms, the aim of study was to investigate the effects vitamin D3 on mtDNA copy number, mitochondrial biogenesis, and membrane integrity of granulosa cells a PCOS-induced mouse model. Materials and Methods: In this experimental study, the PCOS mouse model was induced by dehydroepiandrosterone (DHEA). Granulosa cells after identification by follicle-stimulating hormone receptor (FSHR) were cultured in three groups: 1. granulosa cells treated with vitamin D3 (100 nM for 24 hours), 2. granulosa cells without any treatments, 3. Non-PCOS granulosa cells (control group). Mitochondrial biogenesis gene (TFAM) expression was compared between different groups using real-time PCR. mtDNA copy number was also investigated by qPCR. The mitochondrial structure was evaluated by transmission electron microscopy (TEM). Hormonal levels were measured by enzymelinked immunosorbent assay (ELISA) kit. Results: The numbers of pre-antral and antral follicles increased in PCOS group in comparison with the non-PCOS group. Mitochondrial biogenesis genes were downregulated in granulosa cells of PCOS mice when compared to the non-PCOS granulosa cells. However, treatment with vitamin D3 increased mtDNA expression levels of these genes compared to PCOS granulosa cells with no treatments. Most of the mitochondria in the PCOS group were spherical with almost no cristae. Our results showed that in the PCOS group treated with vitamin D3, the mtDNA copy number increased significantly in comparison to PCOS granulosa cells with no treatments. Conclusion: According to this study, we can conclude, vitamin D3 improves mitochondrial biogenesis and membrane integrity, mtDNA copy number in granulosa cells of PCOS mice which might improve follicular development and subsequently oocyte quality. [ABSTRACT FROM AUTHOR]

Chemical markers in otoliths have been used to assess the stock structure of many marine fishes, but these natural markers have yet to be widely evaluated in the spines of sturgeon fishes in the Caspian Sea, which has six endangered sturgeon species. We used inductively coupled plasma mass spectrometry to quantify B, Ba, Ca, Cu, Fe, Li, Mg, Mn, Si, Sr, and Zn in pectoral fin spines of starry sturgeon (Acipenser stellatus) in the northern and southern Caspian Sea, where depth, salinity, and temperature vary from north to south. Fin spines showed significant regional differences in B/Ca, Cu/Ca, Mn/Ca, Si/Ca, Sr/Ca, and Zn/Ca (Scheirer–Ray–Hare test, p < 0.05). Principal component analysis indicated distinct north/south groups when considering all significant elements in ratio to calcium. The centroids of these regional groups differed significantly (PERMANOVA, p < 0.05). Flexible discriminant analysis classified 85.3% of fish into their correct regions using all element-to-calcium ratios. These results suggest that individuals in different regions share common lifetime environmental histories and may represent unique stocks in the Caspian Sea. Moreover, the findings suggest that pectoral fin-spine microchemistry can be used to identify stocks of starry sturgeon, thus providing a non-lethal approach to elucidating life-history details that are critical to the comprehensive management of sturgeon resources. • A suite of useful microelements revealed in starry sturgeon fin spines. • Sturgeon spine microchemistry differs significantly in north and south Caspian Sea. • Microchemistry suggests regional environmental and physiological differences. • Life-history differences imply unique sturgeon stocks; require management actions. • Fin-spine microchemistry can non-lethally discriminate sturgeon stocks. [ABSTRACT FROM AUTHOR]

Summary: The effect of two feeding rates (0.5 and 1.5% of total body weight) was assessed on the growth of pectoral fin spines of captive juvenile great sturgeon, Huso huso, after second year of life. The fish received Oxytetracycline (OTC) twice in the first and second years of their lives under basic diet. During the 5‐month experimental period, juveniles (mean 1,187.4 g, 0.1 standard deviation [SD]), n = 50) were reared with two feeding rates under similar conditions in 10 fiberglass tanks (1.5 m3). The fish were fed manually with a commercial diet twice a day (35% Biomar, Nersac, France) throughout the experiment. The OTC marks were distinguished in all pectoral fin spine sections under ultraviolet light. The means of the first and second annular radii were 806.6 µm (27.2 SD) and 2,246.5 µm (50.2 SD), respectively. The marginal increment analysis beyond the second OTC mark revealed a significantly smaller marginal increment for low feeding rate treatment (143.9, 11.2 SD) as compared to the high feeding rate one (269.0, 14.6 SD). The results indicate the slower growth rate in the fish fed the low feeding treatments seen in the pectoral fin spine formation, which can be used as an indicator of recent feeding history in sturgeon juveniles. The best daily feeding rate for great sturgeon of 2,460 g was determined to be 1.5% body weight/day in this study. [ABSTRACT FROM AUTHOR]

The morphology of the sagittal otolith of Great sturgeon (Huso huso), Persian sturgeon (Acipenser persicus) and starry sturgeon (Acipenser stellatus) species from the Iranian waters of the Caspian Sea were studied. Three otolith measurements and three shape indices were recorded from 90 sturgeon specimens. Fish biometry traits were measured and relationship between sagittal otolith length (OL)-total length (TL), and sagittal otolith weight (WO)-body weight of fish (BW) were estimated. Sagittal otolith has a triangle shape with irregular edges in great sturgeon, elongate triangle with smooth surfaces in Persian sturgeon, and relatively circular with smooth surface in starry sturgeon. The ratio of the WO/BW in starry sturgeon was significantly higher (P <0.05) than great sturgeon and Persian sturgeon. There is a direct proportional relationship between BW and WO in Persian sturgeon (r²=0.7), great sturgeon (r²=0.9) and starry sturgeon (r²=0.9). Regression line slope for these relationships in starry sturgeon were less than Persian sturgeon and great sturgeon. Furthermore, there is significant linear regression between OL-TL. Results showed that it is possible to identify Caspian sturgeon species based on body morphometry and sagittal otolith characteristics. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder in reproductive‐aged women. Hormonal abnormality caused by steroidogenesis disturbances appears to be the main culprit of the clinical picture in PCOS. Vitamin D3 could regulate steroidogenesis in granulosa cells, but the mechanism of action of vitamin D3 on steroidogenesis remains unknown. AMP‐activated protein kinase (AMPK) has a modulating role in steroid hormone production. We investigated the effect of vitamin D3 on steroidogenesis in cultured granulosa cells of dehydroepiandrosterone‐induced PCOS mice and studied the involvement of AMPK signalling pathway in the current process. Immunoblotting assay showed that vitamin D3 could increase phosphorylation of AMPK alpha and acetyl‐CoA carboxylase, main substrate of AMPK. Vitamin D3 and 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐riboside or Aicar (AMPK activator) not only reduced gene expression of steroidogenic enzymes (P450scc or Cyp11a1, StAR, Cyp19a1 and 3B‐HSD), but also reduced production of progesterone and 17B‐estradiol assessed by radioimmunoassay. Pretreatment with compound C (AMPK inhibitor) decreased APMK phosphorylation and eliminated the effects of vitamin D3 and Aicar on steroidogenic enzymes expression and estradiol and progesterone production. This study showed that vitamin D3 has the main role in regulating of steroidogenesis in granulosa cells of mouse polycystic ovary through activation of the AMPK signalling pathway. Significance of the Study: Polycystic ovarian syndrome (PCOS) is an endocrine disorder of women in reproductive age. This disorder is partly related to disruption in steroidogenesis pathway and dysregulation of estradiol and progesterone production in granulosa cells of polycystic ovaries. Previously, we have shown that vitamin D3 could modulate steroidogenesis pathway in PCOS granulosa cells. In this study, we investigate the molecular mechanism of vitamin D3 in regulation of steroidogenesis pathway. We have shown that vitamin D3 has a modulating role in steroidogenesis pathway of granulosa cells by regulation of AMP‐activated protein kinase (AMPK) as an underlying molecular mechanism in mouse polycystic ovary. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovarian syndrome (PCOS) is a metabolic and endocrine disorder which is characterized by hyperandrogenism, anovulation or oligomenorrhea and polycystic ovarian morphology. It is believed that modulation in metabolism of granulosa cells of PCOS patients may lead to infertility. One of the metabolic modulators is FNDC5 and its cleaved form, irisin. The axis of PGC1α- FNDC5 pathway is one of the main factors affecting cellular energy balance the purpose of this study was to evaluate this pathway in granulosa cells derived from PCOS mice model in comparison with control group. Methods: In the present study, PCOS mouse model was developed by injection of dehydroepiandrosterone (DHEA) hormone in 20 mice for a period of 20 days. Also, 20 uninjected mice were used as the control. Meanwhile, a vehicle group consisted of mice which received daily subcutaneous sesame oil injection (n=20). Relative expressions of PGC1α and FNDC5 in granulosa cells were evaluated by RT-qPCR. Analysis of gene expressions was calculated by the ΔΔCT method and the relative levels of mRNA were normalized to GAPDH transcript levels. Differences in genes expression among three groups were assessed using one-way ANOVA, Tukey's Post Hoc test. Results: Our results showed that expression of FNDC5 was significantly reduced in granulosa cells of DHEA-induced PCOS mice compared with control and vehicle groups (p<0.05), while there was no significant differences in PGC1α expression among different groups. Conclusion: Down regulation of FNDC5 transcript level may contribute in metabolic disturbance of granulosa cells derived from PCOS ovary apart from PGC1α levels which remained unchanged. [ABSTRACT FROM AUTHOR]

In this paper, we study the number of limit cycles in the family d H − ε ω = 0 , where H = y 2 2 − ∫ 0 x g ( u ) d u , ω = y f ( x ) d x , with g ( x ) = x ( x 2 − 1 ) ( x 2 − 1 4 ) 2 , and f ( x ) an even polynomial of degree 10. We will consider mainly the bifurcation of limit cycles near the eye-figure loop and the center of d H = 0 . Our investigation focuses on the lower bound of the maximal number of limit cycles for these systems. In particular, we show that the perturbed system can have at least 8 limit cycles when deg ⁡ ( f ( x ) ) = 10 . [ABSTRACT FROM AUTHOR]

This study reveals the diet of pike-perch from two habitats within the Tersko-Caspian region. The feeding habits of pike-perch in the Sulak and Terek rivers and Tersko-Caspian region were investigated based on 354 specimens sampled monthly from a commercial catch in 2019. Their diet consisted of different prey, with fish representing the most important prey group (up to 90%). Rutilus caspicus dominated with a frequency of occurrence of 20.5, and Aspius aspius, Perca fluviatilis, and Chondrostoma oxyrhynchum, had 13, 9.5, and 8.3%. In the earlier ages 1+ and 2+, zooplankton dominated, followed by mysids and chironomids, which continues into the older ages but at decreasing rates. Analysis of monthly variations in stomach fullness indicated that feeding intensity fluctuated in time, with the highest values in March–April, and lowest in September and November. It was found that the diet of pike-perch in the western Caspian changed considerably from season to season. They begin to actively feed after wintering and before, or even during, spawning period. The spectrum of the diet of Sander lucioperca includes more than 20 elements, mainly juveniles of commercially valuable fish. This fish is characterized by a relatively low ontogenetic diet diversity and flexibility, which makes it sensitive to environmental changes, including anthropogenically induced ones. This fish partially compensates for this disadvantage with its lifestyle, namely, its active foraging movements and migrations from fresh water to salt water and back, following its prey species. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells. In the present study, we investigated the effects of vitamin D3 on steroidogenic enzyme expression and activities in granulosa cell using a PCOS mouse model. In our study, the PCOS mouse model was developed by the injection of dehydroepiandrosterone (DHEA) for 20 days. The mRNA and protein expression levels of genes involved in steroidogenesis in granulosa cells were compared between polycystic and normal ovaries using real-time PCR and Western blotting assays. Granulosa cells of DHEA-induced PCOS mice were then cultured with and without vitamin D3 and mRNA and protein expression levels of steroidogenic enzymes and serum 17beta-estradiol and progesterone levels were investigated using qRT-PCR, western blot, and radioimmunoassay, respectively. Steroidogenic enzymes includingCyp11a1, StAR, Cyp19a1, and3β-HSDwere upregulated in granulosa cells of PCOS mice when compared to normal mice. Treatment with vitamin D3 decreased mRNA and protein expression levels of steroidogenic enzymes in cultured granulosa cells. Vitamin D3 also decreased aromatase and 3β-HSD activity that leads to decreased 17beta-estradiol and progesterone release. This study suggests that vitamin D3 could modulate the steroidogenesis pathway in granulosa cells of PCOS mice that may lead to improving follicular development and maturation. This is a step towards a possible conceivable treatment for PCOS. Abbreviations:AMHR-II: anti-müllerian hormone receptor-II; 3β-HSD: 3β-hydroxysteroid dehydrogenase; Cyp11a1: Cytochrome P450 Family 11 Subfamily A Member 1; Cyp19a1: cytochrome P450 aromatase; DHEA: dehydroepiandrosterone; FSH: follicle stimulating hormone; FSHR: follicle stimulating hormone receptor; IVF:in vitrofertilization; 25OHD: 25-hydroxy vitamin D; OHSS: ovarian hyperstimulation syndrome; PCOS: polycystic ovarian syndrome; P450scc: P450 side-chain cleavage enzyme; StAR: steroidogenic acute regulatory protein; VDRs: vitamin D receptors [ABSTRACT FROM PUBLISHER]

In this paper, the asymptotic expansion of first-order Melnikov function of a heteroclinic loop connecting a cusp of order two and a hyperbolic saddle for a planar near-Hamiltonian system is given. Next, we consider the limit cycle bifurcations of a hyper-elliptic Liénard system with this kind of heteroclinic loop and study the least upper bound of limit cycles bifurcated from the period annulus inside the heteroclinic loop, from the heteroclinic loop itself and the center. We find that at most three limit cycles can be bifurcated from the period annulus, also we present different distributions of bifurcated limit cycles. [ABSTRACT FROM AUTHOR]

The present study investigated basic statistics for biometric traits as well as non-genetic factors that may affect these traits in the Moghani breed of sheep. The data-set was computed by using biometric records of the Moghani sheep breeding and raising station over a period of 15 years (1996 to 2012). Year of birth, month of birth, birth type and lamb's sex and dam permanent environment were considered as the nongenetic factors. The studied biometric traits were: height at withers (HW), height at rump (HR), body length (BL), heart girth (HG) and leg circumference (LC). Least square means (cm) ± standard error were 69.8 ± 4.1, 69.7 ± 4.2, 50.2 ± 4.6, 85.9 ± 8.2 and 29.0 ± 5.4 for HW, HR, BL, HG and LC, respectively. All traits were affected significantly (P<0.05) by the fixed effect of year of birth. The lamb's sex had a significant effect (P<0.001) on the investigated traits except HG. The traits were affected significantly (P<0.001) by the birth type and month of birth. The maternal permanent environment as a non-genetic factor had no significant effect on the traits under study. The results of the present study suggested that non-genetic factors can be considered as notable sources of variation in the biometric traits. Therefore, improving environmental conditions can be suggested if an improvement in the biometric traits of Moghani sheep is desired. [ABSTRACT FROM AUTHOR]

In this work, we study the Abelian integral corresponding to the following Liénard system, where , and are real bounded parameters. By using the expansion of and a new algebraic criterion developed in [Grau et al., 2011], it will be shown that the sharp upper bound of the maximal number of isolated zeros of is 4. Hence, the above system can have at most four limit cycles bifurcating from the corresponding period annulus. Moreover, the configuration (distribution) of the limit cycles is also determined. The results obtained are new for this kind of Liénard system. [ABSTRACT FROM AUTHOR]

The present study aimed to estimate the genetic parameters as well as genetic trends for biometric traits in Iranian Moghani-sheep breeds. The data set consisted of 15115 biometric records from 3702 individual progenies of 499 sires and 3203 dams, which involved a period of 15 years of time (1996–2011). The records were extracted from Moghani sheep breeding and raising station. The studied traits were: height at withers (HW), height at rump (HR), body length (BL), heart girth (HG) and leg circumference (LC). variance components and genetic parameters were estimated with single and five-trait analysis using restricted maximum likelihood (REML)-methods and WOMBAT software. Six different animal models were fitted to the traits, with the best model for each trait determined by Akaike Information Criterion (AIC). All traits were significantly influenced by year of birth, month of birth, sex of the lamb and birth type ( P < 0.01). The breeding values were compared across years of birth with respect to the genetic trends. Direct heritabilities using single trait analysis were estimated 0.10 for HW, 0.11 for HR, 0.16 for BL, 0.11 for HG and 0.23 for LC. Using bivariate analysis, the estimates of additive genetic correlations were ranged from −0.55 (between BL and LC) to 0.99 (between HW and HR). Estimates of breeding value by year of birth for all traits were fluctuated throughout the period of study. Estimates of genetic parameters as well as the estimates of breeding values suggested that the genetic selection can lead to a significant genetic improvement of the Moghani sheep. [ABSTRACT FROM AUTHOR]

Background and aims: P19 cells are a line of pluripotent embryonal carcinoma stem cells, that are able to grow continuously in serum-supplemented media and can be induced to differentiate into all three lineages, mesoderm, endoderm and ectoderm. The sequence of foreign DNA can be introduced into these cells using of standard methods of transfection, through which to examine the cell function and differentiation. This study aimed to induce neuronal phenotype in P19 cells transfected with green fluorescent protein (GFP) gene, using an antiparkinson drug, deprenyl. Methods: In this laboratory descriptive study, calcium phosphate precipitation method was used to introduce pML8 plasmid, encoding GFP and puromycin resistance gene, into these cells. The cells were cultured using MEM-A medium, supplemented with 15% fetal bovine serum. Here 108 M concentrations of deprenyl was used to induce embryoid body differentiation to neuronal lineage. Cresyl violet staining was used to evaluate the morphology of differentiated P19 cells. In addition, immunofluorescence techniques was used to evaluate neuron specific proteins, synaptophysin and β-III tubulin. Results: In addition to production of stable transfected P19 cells, neuronal differentiation of these cells was carried out by the effect of deprenyl induction. GFP-positive neurons derived from embryonic carcinoma cells expressed neuron specific markers. Conclusions: GFP-positive differentiated cells can be used in transplantation studies and basic researches in association with cell therapy and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The morphological characteristics of the pectoral fin spine were compared in three species of sturgeon, the Persian sturgeon ( Acipenser persicus), the Russian sturgeon ( Acipenser gueldenstaedtii), and the Starry sturgeon ( Acipenser stellatus), all sampled from the Caspian Sea. On the basis of morphological characters of the pectoral fin spine, 62.2% of the individuals were correctly classified into separate groups. The cluster analysis also divided the three species into two major subgroups. Acipenser persicus and A. gueldenstaedtii were grouped together, suggesting a similar evolutionary basis. Significant morphological heterogeneity in pectoral fin spine characteristics was observed among the three sturgeon species. Principal component analysis identified the largest differences were in the pectoral fin spine size and the angle between distal pectoral fin spine and the horizontal line ( A°). The first and second principal components ( PC1 and PC2) of all observations accounted for 64.19% and 14.33% of the total variation, respectively. The combination of all analyses showed the relevance of applying pectoral fin spine shape for interspecific distinction of the three species of sturgeons. [ABSTRACT FROM AUTHOR]

• Fin ray chemistry applied for identifying the source of hatchery Persian sturgeon. • Laser ablation split stream ICP-MS/MC ICP-MS applied for the first time to fin rays. • Results contribute to an improved management of Persian sturgeon populations. • Methodological improvements allow for a detailed life-time analysis of sturgeons. Trace elements integrated into fish fin rays from the ambient environment may represent a permanent record of the environmental conditions that an individual has experienced throughout its lifetime. Fish from hatcheries used for stocking may therefore carry a natural intrinsic tag of their origin, which can be then later used for assessing the efficiency of stocking measures. This study investigated the potential of the elemental and strontium isotope (n (87Sr)/ n (86Sr)) composition of fin rays of juvenile Persian sturgeons (Acipenser persicus) to determine their origin. Water and pectoral fin ray samples of twenty age-0 juvenile Persian sturgeons were collected from the largest hatcheries in the east and west of the Southern Caspian Sea region. The elemental content and the Sr isotope ratio in water were determined by (multi collector) inductively coupled plasma mass spectrometry ((MC) ICP-MS), while the elemental content in fin rays (Ba, K, Mg, Mn, Na, Sr) together with the Sr isotope ratio were determined using laser ablation split stream ICP-MS/MC ICP-MS. The elemental composition of Al, B, Ba, Ca, Cu, Fe, Ga, Li, Mg, Mn, Mo, Na, Pb, Rb, Sr, Tl, U and Zn and the Sr isotope ratio of water differed between the investigated hatcheries from the east and west of the Southern Caspian Sea region. Fin rays reflected the elemental (Sr, Ba and Mn) and the Sr isotope composition of pool water of their hatchery of origin. A factor analysis yielded one main factor (high in Sr content and in the n (87Sr)/ n (86Sr) ratio and low in Ba and Mn content) discriminating fin ray samples between sites explaining 86 % of the variation. A discrimination analysis by cross-validated classification yielded 100 % correct assignments of fin ray samples to the hatchery sites using all different parameter combinations. These results suggested that the Sr, Ba Mn elemental and Sr isotope composition of fin rays can be used for the determination of the source hatchery of stocked fish. This represents a valuable tool for evaluation restocking measures of Persian sturgeons in the Southern Caspian Sea region. [ABSTRACT FROM AUTHOR]

We consider the discontinuous piecewise differential equations of the form ( d x 1 d t d x 2 d t ) = { a 0 (t) + a 1 (t) x 1 +.... + a n (t) x 1 n , if 0 ⩽ t ⩽ π , b 0 (t) + b 1 (t) x 2 +.... + b m (t) x 2 m , if π ⩽ t ⩽ 2 π , where a 0 (t) , a 1 (t) ,... , a n (t) and b 0 (t) , b 1 (t) ,... , b m (t) are 2 π -periodic functions in the variable t , and we study the number of limit cycles of such equations on the cylinder. In this way we give exact bounds for the maximum number of limit cycles that the piecewise differential equations have in function of n and m. Note that usually the discontinuous piecewise differential systems are discontinuous in the dependent variable, here the system is discontinuous in the independent variable. [ABSTRACT FROM AUTHOR]

• This is the first study for evaluating the meta-analysis of GWAS and gene network analysis across countries for milk production traits in Holstein cows. • 770 significant SNPs associated with milk production traits were detected across countries. • The most significant lead SNPs for milk production traits were identified on BTA14. These SNPs were rs109421300 SNP near the DGAT1 gene, rs109146371 SNP near the PPP1R16A gene, rs134432442 SNP near the CPSF1 gene, rs109968515 SNP near the CYHR1 gene, and rs111018678 SNP near the TRAPPC9 gene. • Lead SNPs with pleiotropic effects for milk production traits (e.g., rs109421300 and rs109350371 SNPs) were detected in multi-trait meta-analysis. • Regulation of cation channel activity, ion channel complex, and phosphoric diester hydrolase activity were the most significant enriched GO terms for milk production traits. A large number of genome-wide association studies (GWAS) in livestock, especially in dairy cows, provide favorable conditions to integrate multiple independent studies. Methods such as meta-analysis provide the identification of effective QTLs with higher precision and power. A meta-analysis for milk production traits between different countries was conducted using the GWAS summary statistics (i.e., P-value, sample size, allele effects, and etc.) in Holstein cows. In the present study, METAL software was used for the weighted Z-score model. Gene network analysis was used as a complementary method to improve our knowledge of the genome structure of milk production traits and was implemented through the STRING plug-in in Cytoscape software. The Cytoscape ClueGO plug-in was also used for GO enrichment in order to identify biological process, cellular component, and molecular function associated with genomic regions. The aim of this study was to improve the power of QTLs detection and identify the biological mechanisms associated with milk production traits. Data were obtained from 26 published studies from 2010 to 2019. A total of 2,072 SNPs were identified for milk production traits, of which 1,583 SNPs were significant (P < 0.05). Meta-analysis identified 9 QTLs for milk yield, 36 QTLs for fat percentage, and 10 QTLs for protein percentage. Some QTLs were confirmed on BTA14, e.g., BTA14:1801116 close to the DGAT1 gene (milk yield, P = 2.6 × 10 − 131 ; fat percentage, P = 4.8 × 10 − 347 ; protein percentage, P = 7.6 × 10 − 24 ) and BTA14:1651311 close to the PPP1R16A gene (milk yield, P = 2.3 × 10 − 162 ; fat percentage, P = 3.5 × 10 − 153 ). We identified pleiotropic effects of lead SNPs for milk production traits, e.g., one SNP (rs109421300) at BTA14 had pleiotropic effects on milk yield, fat percentage, and protein percentage traits. The most important SNPs for studied traits across countries implicated to network scoring and visualization were including: rs109421300 (DGAT1 gene) for milk yield, fat percentage, and protein percentage; rs109146371 (PPP1R16A gene) for milk yield and fat percentage; rs109968515 (CYHR1 gene) for milk yield and fat percentage; rs134432442 (CPSF1 gene) for fat percentage; rs111018678 (TRAPPC9 gene) for protein percentage. Significant pathways involved in milk production traits through GO term enrichment analysis for biological process, cellular component, and molecular function included: regulation of cation channel activity (P = 1.6 × 10 − 2 ), ion channel complex (P = 1.4 × 10 − 2 ), and phosphoric diester hydrolase activity (P = 1.1 × 10 − 3 ) for milk yield; negative regulation of organ growth (P = 8.2 × 10 − 3 ), transmembrane transporter complex (P = 1.6 × 10 − 3 ), and potassium ion transmembrane transporter activity (P = 8.8 × 10 − 3 ) for fat percentage; mRNA polyadenylation (P = 1.2 × 10 − 2 ), mRNA cleavage factor complex (P = 9.8 × 10 − 4 ), and phosphoric diester hydrolase activity (P = 5.3 × 10 − 3 ) for protein percentage, respectively. Thus, the combination of GWAS summary statistics through a powerful methodology such as meta-analysis will assist us to accurately identify QTLs, potential candidate genes, and biological mechanisms. This kind of studies will help us to have better understanding of QTL regions and genome structure for milk production traits and improve genomic evaluations in Holstein cows. To the best of our knowledge, this is the first meta-analysis of GWAS and GO enrichment across countries for milk production traits in Holstein cows. [ABSTRACT FROM AUTHOR]

Fisheries management has expanded from a traditional focus to a more holistic model based on a model describing the change in the number of generations of fish under the influence of age-dependent natural mortality and harvesting. We calculated the abundance, biomass, production, natural, total loss and catches from the conditional population of great sturgeon resulting from the replenishment of 1.0 million instances of fingerlings with different rates of linear and weight growth in the period 1931–1975. It was found that the size of fingerlings has the greatest influence on the abundance and biomass of conditional great sturgeon populations formed from juveniles. We found an increase in the length of annuals of 19.3%, with the biomass of the conditional population, its production and catch size increasing by 2.9 times. Thus, cultivation of sturgeon in sturgeon hatcheries (SH) and the release of large sized great sturgeon juveniles into the sea will significantly increase the efficiency of work of the artificial reproduction of stocks. • The growth rate of sturgeon juvenile in the first year of life had effect on the number and biomass. • Size of fingerlings influences the biomass of sturgeon populations formed from juveniles. • The length of fingerlings is fundamental for our understanding of the life history of sturgeon. [ABSTRACT FROM AUTHOR]

The article presents a study on the pectoral fin spine structures of the great sturgeon Huso huso and the ship sturgeon Acipenser nudiventris. It states that all subject fish specimens in the study were obtained from commercial catches at the coastal waters of Iran from October and November 2009. It says that differences in the pectoral fin spines are important for significant determination of its species.

During the three-month closure of clinics and day centers in Iran due to the coronavirus disease 2019 (COVID-19) lockdown, parents of children with Autism Spectrum Disorder (ASD) became solely responsible for their care and education. Although centers maintained telephone contact, it quickly became evident that parents needed more detailed advice and guidance. Staff from 30 daycare centers volunteered to take part in a two-month online support and training course for 336 caregivers of children with ASD of different ages. In addition to the provision of visual and written information, synchronous video sessions were used to coach parents on the learning goals devised for the children. Both qualitative and quantitative data were collected to understand the acceptability of using telepractice and the outcomes achieved. A low dropout rate and positive feedback from parents indicated that they perceived telepractice sessions to be useful. The factors contributing to parents' satisfaction were identified. Although the use of telepractice would be a good alternative for caregivers in any future lockdowns, it could also be used in conjunction with daycare center services to encourage greater parental participation, or with families living in areas with no day centers. Further studies are needed to compare telepractice to usual daycare face-to-face interventions, and to document its impact and cost-effectiveness for parents and children. [ABSTRACT FROM AUTHOR]

In this paper, we study the monotonicity of the ratio of some hyperelliptic integrals of order 7. These integrals are related to the 1-forms y d x , x y d x and defined by the hyperelliptic curves of d H = 0 , with H (x , y) = y 2 + P 7 (x) , where P 7 is a polynomial of degree 7 depending on three parameters α , β and γ. Our results are based on the well-known algebraic criteria. [ABSTRACT FROM AUTHOR]

One goal of fisheries management is to identify stocks and ecophenotypics of individual specimens correctly. Discrimination of Persian sturgeon Acipenser persicus ecophenotypics due to geographic variation was attempted based on calcified anatomical structures. Morphological characteristics of the pectoral fin spine were analysed in stocks from the eastern and western parts of the south Caspian Sea to explore if polymorphism could be discerned between regions within the Caspian Sea using ten key features which were measured. These key features were measured and used for multivariate analysis. Principal component analysis (PCA), discriminant function analysis and cluster analysis were used to visualize differences between regions, to follow any shape differences in the spines and to classify into the groups. On the basis of morphometrics between spines, 82.9% of the individuals were correctly classified into one of the two regions. PCA showed the largest differences between the eastern and western regions were the density and arch of pectoral fin spine. Fish from the eastern region had a heavier and more curved pectoral fin spine when compared to those from the western part. The results from this study indicate that the morphological traits of pectoral fin spine of the Persian sturgeons can be used to discriminate between regions with a reliability rate of about 83%. Therefore, the morphological differences are discernible in spite of the volume of artificial rearing and release of fish in the south. [ABSTRACT FROM AUTHOR]

More research is being conducted on myocardial cell treatments utilizing stem cell lines that can develop into cardiomyocytes. All of the forms of cardiac illnesses have shown to be quite amenable to treatments using embryonic (ESCs) and induced pluripotent stem cells (iPSCs). In the present study, we reviewed the differentiation of these cell types into cardiomyocytes from an epigenetic standpoint. We also provided a miRNA network that is devoted to the epigenetic commitment of stem cells toward cardiomyocyte cells and related diseases, such as congenital heart defects, comprehensively. Histone acetylation, methylation, DNA alterations, N6-methyladenosine (m6a) RNA methylation, and cardiac mitochondrial mutations are explored as potential tools for precise stem cell differentiation. [ABSTRACT FROM AUTHOR]

Murine P19 embryonal carcinoma (EC) cells are convenient to differentiate into all germ layer derivatives. One of the advantages of P19 cells is that the exogenous DNA can be easily inserted into them. Here, at the first part of this study, we generated stable GFP-expressing P19 cells (P19-GFP+). FACS and western-blot analysis confirmed stable expression of GFP in the cells. We previously demonstrated the efficient induction of neuronal differentiation from mouse ES and EC cells by application of a neuroprotective drug, selegiline In the second part of this study selegiline was used to induce differentiation of P19-GFP+ into stable GFP-expressing neuron-like cells. Cresyl violet staining confirmed neuronal morphology of the differentiated cells. Furthermore, real-time PCR and immunoflourescence approved the expression of neuron specific markers. P19-GFP+ cells were able to survive, migrate and integrated into host tissues when transplanted to developing chick embryo CNS. The obtained live GFP-expressing cells can be used as an abundant source of developmentally pluripotent material for transplantation studies, investigating the cellular and molecular aspects of early differentiation. [ABSTRACT FROM AUTHOR]

In this paper, the charged Higgs contribution in t-channel single top production is studied. The production process is a t-channel single top event with charged Higgs exchange. Therefore the signal is similar with Standard Model single top production in terms of the final state. In the first step, the signal cross section is calculated and compared to the other main production processes which are used for a heavy charged Higgs search at LHC, i.e., $pp\rightarrow t\bar {b}H^{-}$ and $pp\rightarrow H^{+} \rightarrow t\bar {b}$. In the next step, an event generation and analysis is applied on signal and background events, in order to estimate the signal significance. The signal cross section is typically smaller than the associated production ( $t\bar {b}H^{-}$) and resonance production ( $t\bar {b}$) by a factor of 10 and ranges from 10 f b to 1 f b for charged Higgs mass from 200 to 500 GeV at tan β = 50. Due to the small cross section of signal events and large SM background, the signal significance is small even after a dedicated kinematic analysis and selection of events, however, tan β values above 120 can be excluded at an integrated luminosity of 3000 f b. [ABSTRACT FROM AUTHOR]

The search for the heavy charged Higgs ( m H ± > m top ) has been mainly based on the off-shell top pair production process. However, resonance production in s -channel single top events is an important channel to search for this particle. In a previous work, it was shown that this process, i.e., q q ′ → H + → t b ¯ + h.c. , can lead to comparable results to what is already obtained from LHC searches. What was obtained was, however, based on diagonal Yukawa couplings between incoming quarks assuming c s ¯ as the main incoming pair due to the CKM matrix element being close to unity. The aim of this paper is to show that off-diagonal couplings, like c b ¯ , may lead to substantial contributions to the cross section, even if the corresponding CKM matrix element is two orders of magnitude smaller. For this reason, the cross section is calculated for each initial state including all diagonal and off-diagonal terms, and all is finally added together to get the total cross section which is observed to be ∼2.7 times larger than what is obtained from c s ¯ initial state. Results are eventually reflected into 95% C.L. exclusion and 5 σ discovery contours at different integrated luminosities of LHC. A reasonable coverage of the parameter space is obtained by the 95% C.L. exclusion contour. [ABSTRACT FROM AUTHOR]

Purpose: This study compared the effects of a mineral water rich in calcium, magnesium, bicarbonate, and sulfate and a marketed mineral water with a composition similar to that of urban water on the lipid profile of dyslipidemic adults. Methods: In a randomized controlled trial, 32 adults received one liter of "rich mineral water" daily for one month, and 37 adults drank the same amount of normal mineral water for the same period. Changes in lipid profiles were compared separately in each studied group at the end of one month. Results: Results showed that mean cholesterol and low density lipoprotein LDL levels were significantly decreased in both studied groups after one month of drinking mineral water (P<0.05); however, no significant differences in high density lipoprotein (HDL) and triglyceride (TG) levels were seen in either group one month after drinking. There were no statistically significant differences between the "rich mineral water" and the normal mineral water groups in any of the above-mentioned lipid levels ( P>0.05). Conclusion: A one-month intake of mineral water rich in calcium, magnesium bicarbonate, and sulfate decreased cholesterol and LDL levels but not TG or HDL levels in dyslipidemic adults. [ABSTRACT FROM AUTHOR]

Background and Objectives: Prostatitis affects about 16% of men in their lifetime and sometimes leading to prostate cancer. Bacterial infections are the most common causes of prostatitis. Diagnosis of the causative agents of bacterial prostate infections plays an essential role in timely treating and preventing secondary complications. This study isolated bacterial infectious agents in patients' surgical prostate and evaluated them by routine and molecular microbiological methods. Materials and Methods: In this cross-sectional study, 72 prostate biopsy specimens were collected from the Orology Departmen of hospitals of Qazvin University of Medical Sciences. All samples were cultured in aerobic and anaerobic conditions. Antibiotic susceptibility test by Kirby-Bauer standard method was performed for all isolated bacteria. In addition, all isolated bacteria were identified using 16S rDNA PCR and sanger sequencing methods. Also, TaqMan real-time PCR was applied to detect Ureaplasm aurealyticum, Mycoplasma hominins, and Mycoplasma genitalium. Results: In conventional culture method, out of 18 positive samples, 15 samples (83.3%) were Gram-negative bacteria and 3 samples (16.6%) were Gram-positive bacteria, containing Escherichia coli (55.5%), Klebsiella pneumoniae (11.1%), Enterobacter cloacae (5.5%), Pseudomonas aeruginosa (11.1%), Staphylococcus aureus (11.1%), and Enterococcus faecalis (5.5%). The results of molecular identification methods were the same as conventional culture results. Also, four patients were Ureaplasm aurealyticum, and three patients were positive for Mycoplasma hominis. Conclusion: Most bacteria isolated from prostate specimens belonged to the Enterobacteriaceae family, especially Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae. Staphylococcus aureus and Enterococcus faecalis were cocci isolated in the specimens too. Also, Ureaplasma urealyticum, and Mycoplasma hominis were identified in prostatitis. [ABSTRACT FROM AUTHOR]

Mitochondrial disorders are collectively common, genetically heterogeneous disorders in both pediatric and adult populations. They are caused by molecular defects in oxidative phosphorylation, failure of essential bioenergetic supply to mitochondria, and apoptosis. Here, we present three affected individuals from a consanguineous family of Pakistani origin with variable seizures and intellectual disability. Both females display primary ovarian insufficiency (POI), while the male shows abnormal sex hormone levels. We performed whole exome sequencing and identified a recessive missense variant c.694C > T, p.Arg232Cys in TFAM that segregates with disease. TFAM (mitochondrial transcription factor A) is a component of the mitochondrial replisome machinery that maintains mtDNA transcription and replication. In primary dermal fibroblasts, we show depletion of mtDNA and significantly altered mitochondrial function and morphology. Moreover, we observed reduced nucleoid numbers with significant changes in nucleoid size or shape in fibroblasts from an affected individual compared to controls. We also investigated the effect of tfam impairment in zebrafish; homozygous tfam mutants carrying an in-frame c.141_149 deletion recapitulate the mtDNA depletion and ovarian dysgenesis phenotypes observed in affected humans. Together, our genetic and functional data confirm that TFAM plays a pivotal role in gonad development and expands the repertoire of mitochondrial disease phenotypes. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are a heterogeneous population of adult stem cells, which are multipotent and possess the ability to differentiate/transdifferentiate into mesodermal and nonmesodermal cell lineages. MSCs display broad immunomodulatory properties since they are capable of secreting growth factors and chemotactic cytokines. Safety, accessibility, and isolation from patients without ethical concern make MSCs valuable sources for cell therapy approaches in autoimmune, inflammatory, and degenerative diseases. Many studies have been conducted on the application of MSCs as a new therapy, but it seems that a low percentage of them is related to clinical trials, especially completed clinical trials. Considering the importance of clinical trials to develop this type of therapy as a new treatment, the current paper is aimed at describing characteristics of MSCs and reviewing relevant clinical studies registered on the NIH database during 2016-2020 to discuss recent advances on MSC-based therapeutic approaches being used in different diseases. [ABSTRACT FROM AUTHOR]

Biochemical and physical modifications during the freeze-thaw process adversely influence the restoration of energy-dependent sperm functions required for fertilization. Resveratrol, a phytoalexin, has been introduced to activate 5′ AMP-activated protein kinase which is a cell energy sensor and a cell metabolism regulator. The cryoprotection of resveratrol on sperm cryoinjury via activation of AMP-activated protein kinase also remains to be elucidated. Our aim, thus, was to investigate: (i) the presence and intracellular localization of AMP-activated protein kinase protein; (ii) whether resveratrol may exert a protective effect on certain functional properties of fresh and post-thaw human spermatozoa through modulation of AMP-activated protein kinase. Spermatozoa from normozoospermic men were incubated with or without different concentrations of Compound C as an AMP-activated protein kinase inhibitor or resveratrol as an AMP-activated protein kinase activator for different lengths of time and were then cryopreserved. AMP-activated protein kinase is expressed essentially in the entire flagellum and the post-equatorial region. Viability of fresh spermatozoa was not significantly affected by the presence of Compound C or resveratrol. However, although Compound C caused a potent inhibition of spermatozoa motility parameters, resveratrol did not induce negative effect, except a significant reduction in motility at 25 μ m for 1 h. Furthermore, resveratrol significantly increased AMP-activated protein kinase phosphorylation and mitochondrial membrane potential and decreased reactive oxygen species and apoptosis-like changes in frozen-thawed spermatozoa. Nevertheless, it was not able to compensate decreased sperm viability and motility parameters following cryopreservation. In contrast, Compound C showed opposite effects to resveratrol on AMP-activated protein kinase phosphorylation, reactive oxygen species, apoptosis-like changes, mitochondrial membrane potential, and motility parameters. These findings, although preliminary, suggest that resveratrol-induced improvement of cryopreserved sperm functions may be mediated through activation of AMP-activated protein kinase, indicating the importance of AMP-activated protein kinase activity for human spermatozoa functions. Further investigations are required to elucidate the mechanism by which resveratrol ameliorates oxidative stress-mediated damages in an AMP-activated protein kinase-dependent mechanism. [ABSTRACT FROM AUTHOR]