Does seminal plasma affect angiogenesis in the porcine oviduct?

In the present study we examined the effect of seminal plasma (SP) on angiogenesis in the porcine oviduct. Gene expressions of vascular endothelial growth factor (VEGF) and its two receptors (Flt-1: fms-like tyrosine kinase and Flk-1/KDR: fetal liver kinase-1/kinase insert domain-containing receptor) as well as fibroblast growth factors (FGF-1 and 2) and von Willenbrand factor (VWF) were determined in the oviduct of SP-treated and control (PBS-treated) gilts. Moreover, vascular density (VD) indicated by endothelial cell area immunolocalized by VWF staining, was assessed in the oviducts. Real-time PCR revealed significantly higher expression of FGF-2 and VWF on day 1 (p < 0.05) after SP administration in comparison to control animals. In contrast, Flt-1 mRNA level on day 1 was lower in SP-treated gilts compared to controls (p < 0.05). In the examined oviductal sections, VD did not differ between control and SP-treated animals. However, in SP-treated animals VD was higher on day 5 than on day 1 (p < 0.05) or 3 (p < 0.01). SP had no significant effect on VEGF, Flk-1/KDR and FGF-1 mRNA expression. In conclusion, our results suggest that SP affects the vascular network by changing the expression of factors contributing to angiogenesis.     

Is endocan a novel potential biomarker of liver steatosis and fibrosis?

BackgroundStudies that evaluated endocan levels in nonalcoholic fatty liver disease (NAFLD) and liver fibrosis are scarce. We aimed to explore endocan levels in relation to different stages of liver diseases, such as NAFLD, as determined with fatty liver index (FLI) and liver fibrosis, as assessed with BARD score.MethodsA total of 147 participants with FLI≥60 were compared with 64 participants with FLI <30. An FLI score was calculated using waist circumference, body mass index, gamma-glutamyl transferase and triglycerides. Patients with FLI≥60 were further divided into those with no/mild fibrosis (BARD score 0-1 point; n=23) and advanced fibrosis (BARD score 2-4 points; n=124). BARD score was calculated as follows: diabetes mellitus (1 point) + body mass index≥28 kg/m2 (1 point) + aspartate amino transferase/alanine aminotransferase ratio≥0.8 (2 points).ResultsEndocan was independent predictor for FLI and BARD score, both in univariate [OR=1.255 (95% CI= 1.104-1.426), P=0.001; OR=1.208 (95% CI=1.029-1.419), P=0.021, respectively] and multivariate binary logistic regression analysis [OR=1.287 (95% CI=1.055-1.570), P=0.013; OR=1.226 (95% CI=1.022-1.470), P=0.028, respectively]. Endocan as a single predictor showed poor discriminatory capability for steatosis/fibrosis [AUC=0.648; (95% CI=0.568-0.727), P=0.002; AUC= 0.667 (95% CI=0.555-0.778), P=0.013, respectively], whereas in a Model, endocan showed an excellent clinical accuracy [AUC=0.930; (95% CI=0.886-0.975), P<0.001, AUC=0.840 (95% CI=0.763-0.918), P<0.001, respectively].ConclusionsEndocan independently correlated with both FLI and BARD score. However, when tested in models (with other biomarkers), endocan showed better discriminatory ability for liver steatosis/fibrosis, instead of its usage as a single biomarker.     

TWEAK: a novel biomarker for lupus nephritis?

Renal involvement is common in systemic lupus erythematosus. Early diagnosis of lupus nephritis (LN), allowing the instigation of appropriate therapy, remains an important clinical challenge. Current biomarkers in clinical practice are less than ideal, lacking both sensitivity and specificity. In the previous issue of Arthritis Research & Therapy, Schwartz and colleagues demonstrated the potential value of urinary TNF-like weak inducer of apoptosis (uTWEAK) as a biomarker for LN. They showed that uTWEAK is elevated in subjects with LN at diagnosis compared with those with systemic lupus erythematosus but no renal disease, and correlates with the degree of clinical disease activity. These data are thought-provoking and provide the platform for future longer-term studies.     

α-L-fucosidase in the reproductive organs and seminal plasma of the bull

α-L-Fucosidase (EC 3.2.1.51) activity was studied in different reproductive organs, seminal plasma and spermatozoa of the bull. The highest specific activity of α-L-fucosidase was found in the epididymis. Gel filtration at pH 7.0 revealed two α-L-fucosidases (α-L-fucosidase I and α-L-fucosidase II) in most reproductive tissues, but seminal plasma, spermatozoa and epididymal cauda contained only form I. Fractionation at basic pH (pH 8.5) resulted in the elution of α-L-fucosidase as form II. Some differences were encountered in pH profiles and thermal stabilities of the two enzyme forms and they showed additional polymorphism after chromatofocusing. The comparison of enzyme profiles after fractionations suggests that cauda epididymidis is the main source of the seminal plasma activity in the bull.     

Is an ovulation-inducing factor (OIF) present in the seminal plasma of rabbits?

The objectives of this study were (1) to determine the effect of rabbit seminal plasma on LH secretion and ovulation using the llama animal model as an in vivo ovulation bioassay and (2) to determine the effect of llama or rabbit seminal plasma on ovulation induction in the rabbit model. In Experiment 1, llamas with a growing follicle ≥8mm in diameter were assigned randomly to one of three groups (n=5 per group) and given an intramuscular dose of 1mL of: (a) llama seminal plasma, (b) rabbit seminal plasma, or (c) phosphate buffered saline (PBS; negative control). Blood samples for LH measurement were taken every 15 min from 1.5 h before to 8 h after treatment (Day 0: starting of treatment). Llamas were examined by ultrasonography every 12h from treatment to ovulation, and then every other day until Day 16 after treatment to evaluate corpus luteum (CL) development. Blood samples for progesterone measurement were taken every other day from Day 0 to Day 16. Ovulation was detected in 4 of 5, 5 of 5, and 0 of 0 llamas treated with llama or rabbit seminal plasma and PBS, respectively (P<0.001). After treatment, plasma LH concentration increased and decreased (P<0.01) in the llama and rabbit seminal plasma group but not in the PBS-treated group. No differences were observed on CL development (P≥0.3) and progesterone secretion (P>0.05) between both seminal plasma treated groups. In Experiment 2, receptive female rabbits (n=5-7 per group) were given an intramuscular dose of: (a) 0.5, (b) 1.0 and (c) 2.0mL of either rabbit or llama seminal plasma, (d) 0.5mL PBS (negative control), or (e) 25μg of gonadoreline acetate (GnRH; positive control). Does were submitted to laparotomy 24-36 h after treatment to determine the ovulatory response and the presence of antral and hemorrhagic anovulatory follicles. Ovulation sites (7.0±0.6) were only detected in GnRH-treated does (P<0.01). There was an increase (P<0.01), in the total number of follicles (antral plus hemorraghic follicles) in those females treated with 1mL of rabbit seminal plasma and there was a tendency (P=0.08) for more hemorrhagic anovulatory follicles in does treated with 1.0 and 2.0mL of either rabbit or llama seminal plasma. Results document the presence of OIF in the seminal plasma of rabbits. The differential ovulatory response between species, however, requires further investigation.     

Computational analysis of the interactions of a novel cephalosporin derivative with β-lactamases

Background

One of the main concerns of the modern medicine is the frightening spread of antimicrobial resistance caused mainly by the misuse of antibiotics. The researchers worldwide are actively involved in the search for new classes of antibiotics, and for the modification of known molecules in order to face this threatening problem. We have applied a computational approach to predict the interactions between a new cephalosporin derivative containing an additional β-lactam ring with different substituents, and several serine β-lactamases representative of the different classes of this family of enzymes.

Results

The results of the simulations, performed by using a covalent docking approach, has shown that this compound, although able to bind the selected β-lactamases, has a different predicted binding score for the two β-lactam rings, suggesting that one of them could be more resistant to the attack of these enzymes and stay available to perform its bactericidal activity.

Conclusions

The detailed analysis of the complexes obtained by these simulations suggests possible hints to modulate the affinity of this compound towards these enzymes, in order to develop new derivatives with improved features to escape to degradation.

     

Could circRNA be a new biomarker for pre‐eclampsia?

Pre‐eclampsia is a devastating complication of pregnancy which is characterized by hypertension and proteinuria in pregnant women. Pre‐eclampsia is important as it is the leading cause of death. Moreover, untreated pre‐eclampsia might lead to other lethal complications, for both fetus and mother. Pre‐eclampsia can also affect the quality of life in affected women. Despite a large number of risk factors for pre‐eclampsia, these risk factors are able to detect just 30% of women who are susceptible to pre‐eclampsia. Heterogeneous manifestations of pre‐eclampsia necessitate the discovery of potential biomarkers required for its early detection. Circular RNAs (circRNAs) are a type of RNA which are more abundant, specific, and highly organized compared with other types of RNA. Accordingly, circRNAs have been suggested as one of the potential biomarkers for different diseases. Recently, researchers have shown interest in the effects of circRNAs in pre‐eclampsia, although the current evidence is limited. The majority of obstetricians are probably not aware of circRNAs as a useful biomarker. Here, we aimed to summarize recent supporting evidence and assess the mechanisms by which circRNAs are involved in pre‐eclampsia.     

Y chromosome and male infertility: what is a normal Y chromosome?

The human Y chromosome contains a number of genes and gene families that are essential for germ cell development and maintenance. Many of these genes are located in highly repetitive elements that are subject to rearrangements. Deletion of azoospermia factor (AZF) regions AZFa, AZFb, and AZFc are found in approximately 10-15% of men with severe forms of spermatogenic failure. Several partial AZFc deletions have been described. One of these, which removes around half of all the genes within the AZFc region, appears to be present as an inconsequential polymorphism in populations of northern Eurasia. A second deletion, termed gr/gr, also results in the absence of several AZFc genes and it may be a genetic risk factor for spermatogenic failure. However, the link between these partial deletions and fertility is unclear. The gr/gr deletion is not a single deletion but a combination of deletions that vary in size and complexity and result in the absence of different genes. There are also regional or ethnic differences in the frequency of gr/gr deletions. In some Y-chromosome lineages, these deletions appear to be fixed and may have little influence on spermatogenesis. Most of these data (gene content and Y chromosome structure) have been deduced from the reference Y chromosome sequence deposited in NCBI. However, recently there have been attempts to define these types of structural rearrangements in the general population. These have highlighted the considerable degree of structural diversity that exist. Trying to correlate these changes with the phenotypic variability is a major challenge and it is likely that there will not be a single reference (or normal) Y chromosome sequence but many.     

O-GlcNAc glycosylation: a signal for the nuclear transport of cytosolic proteins?

Year 2004 marks the 20th anniversary of the discovery of O-linked N-acetylglucosamine (O-GlcNAc) by Gerald W. Hart. Despite interest for O-GlcNAc, the functions played by this single monosaccharide remain poorly understood, though numerous roles have been suggested, among which is the involvement of O-GlcNAc in the nuclear transport of cytosolic proteins. This idea was first sustained by studies on bovine serum albumin that showed that the protein could be actively carried to the nucleus when it was modified with sugars. In this paper, we will review data on this puzzling problem. We will first describe the well-established nuclear localisation signal (NLS)-dependent nuclear transport by presenting the different factors involved, and then, we will examine where and how O-GlcNAc could be involved in nuclear transport. Whereas it has been suggested that O-GlcNAc could interfere at two levels in the nuclear transport both by modifying proteins to be translocated to the nucleus and by modifying the nucleoporins of the nuclear pore complex, according to us, this second idea seems unlikely. Part of this study will also be dedicated to a relatively new concept in the nuclear transport: the role of the 70-kDa heat shock proteins (HSP70). The action of the chaperone in nuclear translocation was put forward 10 years ago, but new findings suggest that this mechanism could be linked to O-GlcNAc glycosylation.     

Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker?

Fascin is a globular actin cross-linking protein that has a major function in forming parallel actin bundles in cell protrusions that are key specialisations of the plasma membrane for environmental guidance and cell migration. Fascin is widely expressed in mesenchymal tissues and the nervous system and is low or absent in adult epithelia. Recent data from a number of laboratories have highlighted that fascin is up-regulated in many human carcinomas and, in individual tissues, correlates with the clinical aggressiveness of tumours and poor patient survival. In cell culture, over-expression or depletion of fascin modulates cell migration and alters cytoskeletal organisation. The identification of biomarkers to provide more effective early diagnosis of potentially aggressive tumours, or identify tumours susceptible to targeted therapies, is an important goal in clinical research. Here, we discuss the evidence that fascin is upregulated in carcinomas, its contributions to carcinoma cell behaviour and its potential as a candidate novel biomarker or therapeutic target.     

Could shading reduce the negative impacts of drought on coffee? A morphophysiological analysis

Based on indirect evidence, it was previously suggested that shading could attenuate the negative impacts of drought on coffee (Coffea arabica), a tropical crop species native to shady environments. A variety (47) of morphological and physiological traits were examined in plants grown in 30-l pots in either full sunlight or 85% shade for 8 months, after which a 4-month water shortage was implemented. Overall, the traits showed weak or negligible responses to the light × water interaction, explaining less than 10% of the total data variation. Only slight variations in biomass allocation were observed in the combined shade and drought treatment. Differences in relative growth rates were mainly associated with physiological and not with morphological adjustments. In high light, drought constrained the photosynthetic rate through stomatal limitations with no sign of apparent photoinhibition; in low light, such constraints were apparently linked to biochemical factors. Sun-grown plants displayed osmotic adjustments, decreased tissue elasticities and improved long-term water use efficiencies, especially under drought. Regardless of the water availability, higher concentrations of lipids, total phenols, total soluble sugars and lignin were found in high light compared to shade conditions, in contrast to the effects on cellulose and hemicellulose concentrations. Proline concentrations increased in water-deprived plants, particularly those grown under full sun. Phenotypic plasticity was much higher in response to the light than to the water supply. Overall, shading did not alleviate the negative impacts of drought on the coffee tree.     

＂Micro-deletions＂ of the human Y chromosome and their relationship with male infertility

The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes.The human Y chromosome (60 Mb long) is largely composed of repeti-tive sequences that give it a heterochromatic appearance,and it consists of pseudoautosomal,euchromatic,and heterochromatic regions.Located on the two extremities of the Y chromosome,pseudoautosomal regions 1 and 2 (PAR1 and PAR2,2.6 Mb and 320 bp long,re-spectively) are homologs with the termini of the X chromosome.The euchromatic region and some of the repeat-rich heterochromatic parts of the Y chromosome are called "male-specific Y" (MSY),which occupy more than 95% of the whole Y chromosome.After evolu-tion,the Y chromosome becomes the smallest in size with the least number of genes but with the most number of copies of genes that are mostly spermatogenesis-related.The Y chromosome is characterized by highly repetitive sequences (including direct repeats,inverted repeats,and palindromes) and high polymorphism.Several gene rearrangements on the Y chromosome occur during evolution owing to its specific gene structure.The consequences of such rearrangements are not only loss but also gain of specific genes.One hundred and fifty three haplotypes have been discovered in the human Y chromosome.The structure of the Y chromosome in the GenBank belongs to haplotype R1.There are 220 genes (104 coding genes,111 pseudogenes,and 5 other uncategorized genes) according to the most recent count.The 104 coding genes encode a total of about 48 proteins/protein families (including putative proteins/protein families).Among them,16 gene products have been discovered in the azoospermia factor region (AZF) and are related to spermatogenesis.It has been dis-covered that one subset of gene rearrangements on the Y chromosome,"micro-deletions",is a major cause of male infertility in some populations.However,controversies exist about different Y chromosome haplotypes.Six AZFs of the Y chromosome have been discov-ered including AZFa,AZFb,AZFc,and their combinations AZFbc,AZFabc,and partial AZFc called AZFc/gr/gr.Different deletions in AZF lead to different content spermatogenesis loss from teratozoospermia to infertility in different populations depending on their Y hap-lotypes.This article describes the structure of the human Y chromosome and investigates the causes of micro-deletions and their relation-ship with male infertility from the view of chromosome evolution.After analysis of the relationship between AZFc and male infertility,we concluded that spermatogenesis is controlled by a network of genes,which may locate on the Y chromosome,the autochromosomes,or even on the X chromosome.Further investigation of the molecular mechanisms underlying male fertility/infertifity will facilitate our knowledge of functional genomics.     

Class III β-tubulin,a novel biomarker in the human melanocyte lineage

It is generally thought that class III β-tubulin expression is limited to cells of the neural lineage and is therefore often used to identify neurons amongst other cell types, both in vivo and in vitro. Melanocytes are derived from the neural crest and share both morphological features and functional characteristics with peripheral neurons. Here, we show that these similarities extend to class III β-tubulin (TUBB3) expression, and that human melanocytes express this protein both in vivo and in vitro. In addition, we studied the expression of class III β-tubulin in two murine melanogenic cell lines and show that expression of this protein starts as melanoblasts mature into melanocytes. Melanin bleaching experiments revealed close proximity between melanin and TUBB3 proteins. In vitro stimulation of primary human melanocytes by α-MSH indicated separate regulatory mechanisms for melanogenesis and to TUBB3 expression. Together, these observations imply that human melanocytes express TUBB3 and that this protein should be recognized as a wider marker for multiple neural crest-derived cells.     

Consequences of elevating plasma testosterone in females of a socially monogamous songbird: evidence of constraints on male evolution?

To explore whether selection for testosterone-mediated traits in males might be constrained by costs of higher testosterone to females, we examined the effects of experimental elevation of plasma testosterone on physiological, reproductive, and behavioral parameters in a female songbird, the dark-eyed junco (Junco hyemalis). We used subcutaneous implants to elevate testosterone (T) in captive and free-living female juncos. In captive birds, we measured the effects of high T on body mass, feather molt, and brood patch formation. In the field, we monitored its effects on the timing of egg laying, clutch size, egg size, egg steroid levels, incubation, and nest-defense behavior. Females implanted with testosterone (T-females) had significantly higher circulating levels of testosterone than did control females (C-females). Captive T-females had lower body mass, were less likely to develop brood patches, and delayed feather molt relative to C-females. Among free-living females, the interval between nest completion and appearance of the first egg was longer for T-females than for C-females and egg yolk concentrations of testosterone were higher, but there were no significant differences in estradiol levels, clutch size, or egg size. Incubation and nest defense behavior were also similar between T- and C-females. Our results suggest that selection on males for higher testosterone might initially lead to a correlated response in females producing changes in body mass and feather molt, both of which could be detrimental. Other possible female responses would be delayed onset of reproduction, which might reduce reproductive success, and higher yolk testosterone, which might have either positive or negative effects on offspring development. We found no reason to expect reduced parental behavior by females as a negative fitness consequence of selection for higher testosterone in males.     

Müllerian inhibiting substance as a novel biomarker of cisplatin-induced ovarian damage

Müllerian inhibiting substance (MIS) has been investigated as a possible serum biomarker in human aging to estimate the number of female germ cells remaining. Cisplatin is an effective chemotherapeutic agent that is associated with ovarian injury. In this study, we tested the hypothesis that decreasing serum MIS can serve as a biomarker of ovarian damage after cisplatin. Adult female rats were treated with saline, 4.5, or 6.0 mg/kg cisplatin. The serum MIS levels were lower in both cisplatin groups, in a dose-related fashion. The ovarian lysates of both cisplatin groups had less MIS than control. Immunofluorescence analysis showed that the percentage of MIS-positive follicles was lower in the 6.0 mg/kg group. TUNEL assays showed that there was a dose related increase in the number of apoptotic follicles in the cisplatin groups. In summary, a decrease in serum MIS could serve as a biomarker to discriminate the degree of ovarian damage after cisplatin. These data are the first to establish in the rat that ovarian injury due to a chemotherapeutic agent could be monitored with the non-invasive serum biomarker MIS.     

Do bacterial infections cause reduced ejaculate quality? A meta-analysis of antibiotic treatment of male infertility

Ejaculate quality may limit male reproductive success, and consequently,sperm quality is of importance. Spermatozoa are perceived as"non-self" by the immune system and are exposed to immunologicalattacks in the male reproductive tract. To reduce immunologicalreactions against their own sperm, males are dependent on thetestis being an immunoprivileged site. Immunoprivilege is obtainedby the blood-testis barrier and by local immunosuppression byandrogens. Despite this testicular immunosuppression, an influxof leukocytes may occur in testes. The condition in which maleshave a heightened level of leukocytes in semen is called leukocytospermia,and it is associated with reduced fertility. As the abilityof immunosuppression by androgens may depend on current intensitiesof infectious organisms in the extratesticular soma, only maleswith high parasite resistance may be able to bear the cost ofimmunosuppression and consequently produce high quality ejaculates.This issue is addressed by a meta-analysis on the effects ofbroad-spectrum antibiotic treatment of male leukocytospermia-associatedinfertility. The analysis showed that antibiotic treatment ofleukocytospermic men, without diagnosed genital tract infections,resulted in a significant improvement of ejaculate quality,that is, an increase in ejaculate volume, sperm concentration,number of motile spermatozoa, and number of spermatozoa withnormal morphology. Moreover, the amount of leukocytes in semenwas also reduced. This suggests that broad-spectrum treatmenttargeted toward bacterial infections reduces the density ofleukocytes in semen and, at the same time, improves the qualityof ejaculates produced. Our results emphasize the importanceof parasitic resistance and immunity as factors that cause variationsin ejaculate quality.     

Could a dysfunction of ferritin be a determinant factor in the aetiology of some neurodegenerative diseases?

Background

The concentration of iron in the brain increases with aging. Furthermore, it has also been observed that patients suffering from neurological diseases (e.g. Parkinson, Alzheimer…) accumulate iron in the brain regions affected by the disease. Nevertheless, it is still not clear whether this accumulation is the initial cause or a secondary consequence of the disease. Free iron excess may be an oxidative stress source causing cell damage if it is not correctly stored in ferritin cores as a ferric iron oxide redox-inert form.

Scope

Both, the composition of ferritin cores and their location at subcellular level have been studied using analytical transmission electron microscopy in brain tissues from progressive supranuclear palsy (PSP) and Alzheimer disease (AD) patients.

Major conclusions

Ferritin has been mainly found in oligodendrocytes and in dystrophic myelinated axons from the neuropili in AD. In relation to the biomineralization of iron inside the ferritin shell, several different crystalline structures have been observed in the study of physiological and pathological ferritin. Two cubic mixed ferric–ferrous iron oxides are the major components of pathological ferritins whereas ferrihydrite, a hexagonal ferric iron oxide, is the major component of physiological ferritin. We hypothesize a dysfunction of ferritin in its ferroxidase activity.

General significance

The different mineralization of iron inside ferritin may be related to oxidative stress in olygodendrocites, which could affect myelination processes with the consequent perturbation of information transference.