Slow fertilization of stickleback eggs: the result of sexual conflict?

BACKGROUND: The fertilization success in sperm competition in externally fertilizing fish depends on number and quality of sperm. The time delay between sequential ejaculations may further influence the outcome of sperm competition. Such a time interval can load the raffle over fertilization if fertilization takes place very fast. Short fertilization times are generally assumed for externally fertilizing fish such as the three-spined stickleback (Gasterosteus aculeatus). In this pair-spawning fish, territorial males often try to steal fertilizations in nests of neighbouring males. This sneaking behaviour causes sperm competition. Sneakers will only get a share of paternity when eggs are not fertilized immediately after sperm release. Contrary to males, females may be interested in multiple paternity of their clutch of eggs. There thus may be a sexual conflict over the speed of fertilization. RESULTS: In this study we used two different in vitro fertilization experiments to assess how fast eggs are fertilized in sticklebacks. We show that complete fertilization takes more than 5 min which is atypically long for externally fertilizing fishes. CONCLUSION: This result suggests that the time difference does not imply high costs to the second stickleback male to ejaculate. Slow fertilization (and concomitant prolonged longevity of sperm) may be the result of sexual conflict in which females aimed at complete fertilization and/or multiple paternity.

Peripartal progesterone and prolactin have little effect on the rapid transport of immunoglobulin G into colostrum of dairy cows

Colostrum formation and lactogenesis in the mammary gland and the timing of parturition are regulated by endocrine signals. Changes in progesterone (P4) and prolactin (PRL) are considered key events that inhibit colostrum formation, trigger parturition, and signal the onset of lactation. The goal of our study was to determine if colostrum yield and composition and immunoglobulin transfer are affected by prepartum milking relative to the decrease in P4, peak of PRL, or occurrence of parturition. Twenty-three multiparous cows were randomly assigned to 1 of 2 groups: (1) control with first milking at 4h postcalving (CON, n=11), and (2) treatment group with first milking approximately 1d before calving and second milking at 4h after parturition (APM, n=12). Colostrum yields were recorded and proportional samples were analyzed for immunoglobulin G (IgG) concentration. Blood plasma samples for the analyses of P4 and PRL were collected 3 times daily at 8-h intervals for 4d prepartum and again taken at 4h after parturition. Total colostrum mass of APM cows was higher than that of CON cows. Immunoglobulin G concentration and protein content did not differ between antepartum milking in APM cows and postpartum milking in CON cows. Colostrum IgG concentration and protein content in APM cows at the postpartum milking were lower compared with the IgG concentration established at the prepartum (APM) and postpartum milkings of CON cows. Immunoglobulin G mass did not differ in first and second colostrum collection in APM cows but was lower compared with that of CON cows. The sum of IgG mass in APM cows (prepartum + postpartum collections) did not differ from that of CON cows. Lactose and fat in milk (concentration and mass) increased from first to second milking in APM cows. Total mass of lactose and fat in APM cows (prepartum + postpartum collections) was greater compared with that of CON cows. The finding that the time of milking relative to parturition, P4 decrease, and PRL peak slightly affected yield and quality of colostrum emphasizes the complex interactions of numerous endocrine and morphological changes occurring during colostrogenesis and lactogenesis in dairy cows. The considerably rapid transfer of immunoglobulins into colostrum of prepartum-milked cows within a few hours leads to the hypothesis that the transfer of IgG can be very fast and-contrary to earlier findings-persist at least until parturition.

Stereoselective virtual screening of the ZINC database using atom pair 3D-fingerprints

Background Tools to explore large compound databases in search for analogs of query molecules provide a strategically important support in drug discovery to help identify available analogs of any given reference or hit compound by ligand based virtual screening (LBVS). We recently showed that large databases can be formatted for very fast searching with various 2D-fingerprints using the city-block distance as similarity measure, in particular a 2D-atom pair fingerprint (APfp) and the related category extended atom pair fingerprint (Xfp) which efficiently encode molecular shape and pharmacophores, but do not perceive stereochemistry. Here we investigated related 3D-atom pair fingerprints to enable rapid stereoselective searches in the ZINC database (23.2 million 3D structures). Results Molecular fingerprints counting atom pairs at increasing through-space distance intervals were designed using either all atoms (16-bit 3DAPfp) or different atom categories (80-bit 3DXfp). These 3D-fingerprints retrieved molecular shape and pharmacophore analogs (defined by OpenEye ROCS scoring functions) of 110,000 compounds from the Cambridge Structural Database with equal or better accuracy than the 2D-fingerprints APfp and Xfp, and showed comparable performance in recovering actives from decoys in the DUD database. LBVS by 3DXfp or 3DAPfp similarity was stereoselective and gave very different analogs when starting from different diastereomers of the same chiral drug. Results were also different from LBVS with the parent 2D-fingerprints Xfp or APfp. 3D- and 2D-fingerprints also gave very different results in LBVS of folded molecules where through-space distances between atom pairs are much shorter than topological distances. Conclusions 3DAPfp and 3DXfp are suitable for stereoselective searches for shape and pharmacophore analogs of query molecules in large databases. Web-browsers for searching ZINC by 3DAPfp and 3DXfp similarity are accessible at www.gdb.unibe.ch webcite and should provide useful assistance to drug discovery projects.

Radical prostatectomy in very high-risk localized prostate cancer: long-term outcomes and outcome predictors

The objective of this study was to present the long-term outcomes and determine outcome predictors in very high-risk (cT3b-T4) prostate cancer (PCa) after radical prostatectomy (RP).

Predicting prostate cancer-specific outcome after radical prostatectomy among men with very high-risk cT3b/4 PCa: a multi-institutional outcome study of 266 patients

BACKGROUND The value of radical prostatectomy (RP) as an approach for very high-risk prostate cancer (PCa) patients is controversial. To examine the risk of 10-year cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathological characteristics of very high-risk cT3b/4 PCa patients treated with RP as the primary treatment option. METHODS In a multi-institutional cohort, 266 patients with very high-risk cT3b/4 PCa treated with RP were identified. All patients underwent RP and pelvic lymph-node dissection. Competing-risk analyses assessed 10-year CSM and OCM before and after stratification for age and Charlson comorbidity index (CCI). RESULTS Overall, 34 (13%) patients died from PCa and 73 (28%) from OCM. Ten-year CSM and OCM rates ranged from 5.6% to 12.9% and from 10% to 38%, respectively. OCM was the leading cause of death in all subgroups. Age and comorbidities were the main determinants of OCM. In healthy men, CSM rate did not differ among age groups (10-year CSM rate for ⩽64, 65-69 and ⩾70 years: 16.2%, 11.5% and 17.1%, respectively). Men with a CCI ⩾1 showed a very low risk of CSM irrespective of age (10-year CSM: 5.6-6.1%), whereas the 10-year OCM rates increased with age up to 38% in men ⩾70 years. CONCLUSION Very high-risk cT3b/4 PCa represents a heterogeneous group. We revealed overall low CSM rates despite the highly unfavorable clinical disease. For healthy men, CSM was independent of age, supporting RP even for older men. Conversely, less healthy patients had the highest risk of dying from OCM while sharing very low risk of CSM, indicating that this group might not benefit from an aggressive surgical treatment. Outcome after RP as the primary treatment option in cT3b/4 PCa patients is related to age and comorbidity status.

Very long-term survival patterns of young patients treated with radical prostatectomy for high-risk prostate cancer

OBJECTIVE In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. MATERIALS AND METHODS Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. RESULTS The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09). CONCLUSIONS Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.

Annulation of Tetrathiafulvalene to the Bay Region of Perylenediimide: Fast Electron-Transfer Processes in Polar and Nonpolar Solvents

A tetrathiafulvalene donor has been annulated to the bay region of perylenediimide through a 1H-benzo-[d]pyrrolo[1,2-a]imidazol-1-one spacer affording an extended pi-conjugated molecular dyad (TTF-PDI). To gain insight into its ground- and excited-state electronic properties, the reference compound Ph-PDI has been prepared via a direct Schiff-base condensation of N,N'-bis(1-octylnonyl) benzoperylene-1',2':3,4:9,10-hexacarboxylic-1',2'-anhydride-3,4:9,10-bis (imide) with benzene-1,2-diamine. Both the experimental and the computational (DFT) results indicate that TTF-PDI exhibits significant intramolecular electronic interactions giving rise to an efficient photoinduced charge-separation process. Free-energy calculations verify that the process from TTF to the singlet-excited state of PDI is exothermic in both polar and nonpolar solvents. Fast adiabatic electron-transfer processes of a compactly fused, pi-conjugated TTF-PDI dyad in benzonitrile, 2-methyltetrahydrofuran, anisole and toluene were observed by femtosecond transient absorption spectral measurements. The lifetimes of radical-ion pairs slightly increase with decreasing the solvent polarities, suggesting that the charge-recombination occurs in the Marcus inverted region. By utilizing the nanosecond transient absorption technique, the intermolecular electron-transfer process in a mixture of has been observed via the triplet excited PDI for the first time.

Debulking surgery in the setting of very high-risk prostate cancer scenarios

What's known on the subject? and What does the study add? Nowadays radical prostatectomy (RP) is considered an effective treatment in high-risk prostate cancer (PCa) and the indications for a surgical approach are expanding, even in cases of very high PSA or node-positive disease. We explored the outcomes of debulking surgery in the setting of these very high-risk PCa patients, in order to assess its feasibility. This review confirms the important role achieved by surgery in the complex setting of patients with very high-risk PCA. Excellent survival rates have been reported, even when PSA exceeds 100 ng/mL. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Furthermore, salvage RP confirmed to be the most effective treatment option after RT failure. On the contrary, up-to-date surgery of isolated nodal recurrences has shown only little benefit. Finally, there is no evidence supporting the efficacy of debulking surgery in metastatic or in hormone-refractory tumours. An accurate selection of the patient is essential.

Low-grade endometrial stromal sarcoma with inferior vena cava tumor thrombus and intracardiac extension: radical resection may improve recurrence free survival

BACKGROUND: Endometrial stromal sarcoma (ESS) represents 0.2% of all uterine malignancies. Based on the mitotic activity, a distinction is made between low and high-grade ESS. Although the overall five-year survival rate for low-grade ESS exceeds 80%, about 50% of the patients show tumor recurrence, mostly after a long latency period. Tumor invasion of the great vessels is extremely rare. We describe a patient with advanced low-grade ESS with tumor invasion of the infrarenal aorta and the inferior vena cava. The patient presented with a large tumor thrombus extending from the inferior vena cava into the right atrium. METHODS: Review of literature and identification of 19 patients, including our own case report, with advanced low-grade ESS with invasion of the great vessels and formation of an inferior vena cava tumor thrombus. RESULTS: All 19 patients presented with an abdominal tumor mass and a tumor thrombus protruding into the inferior vena cava. The tumor thrombus extended into the right heart cavities in nine patients reaching the right atrium in four, the right ventricle in three and the pulmonary artery in two patients. There were 5 patients with an advanced primary tumor and 14 patients with an advanced recurrent tumor. Seven patients presented with synchronous metastatic disease and six patients with a pelvic tumor infiltrating the bladder, the rectosigmoid colon or the infrarenal aorta. Mean age at surgery was 45.9+/-12.3 years (median 47, range 25-65 years). Tumor thrombectomy was accomplished by cavatomy or by right atriotomy after installation of a cardiopulmonary bypass. There was no peri-operative mortality and a very low morbidity. Radical tumor resections were achieved in 10 patients. The follow-up for these 10 patients was 2+/-1.3 years (median 2, range 0.3-4.5 years). Nine patients remained recurrence free whereas one patient suffered an asymptomatic local recurrence. CONCLUSIONS: Low-grade ESS is a rare angioinvasive tumor with a high recurrence rate. Resection of an inferior vena cava tumor thrombus, even with extension into the right heart cavities, can be performed safely. Extensive radical surgery is therefore justified in the treatment of advanced tumor manifestations of a low-grade ESS potentially improving recurrence free survival.

Using transcranial magnetic stimulation to probe decision-making and memory

Decision-making and memory are fundamental processes for successful human behaviour. For eye movements, the frontal eye fields (FEF), the supplementary eye fields (SEF), the dorsolateral prefrontal cortex (DLPFC), the ventrolateral frontal cortex and the anterior cingulum are important for these cognitive processes. The online approach of transcranial magnetic stimulation (TMS), i.e., the application of magnetic pulses during planning and performance of saccades, allows interfering specifically with information processing of the stimulated region at a very specific time interval (chronometry of cortical processing). The paper presents studies, which showed the different roles of the FEF and DLPFC in antisaccade control. The critical time interval of DLPFC control seems to be before target onset since TMS significantly increased the percentage of antisaccade errors at that time interval. The FEF seems to be important for the triggering of correct antisaccades. Bilateral stimulation of the DLPFC could demonstrate parallel information-processing transfer in spatial working memory during memory-guided saccades.

Fluorescent In Situ hybridization: a new tool for the direct identification and detection of F. psychrophilum

F. psychrophilum is the causative agent of Bacterial Cold Water Disease (BCW) and Rainbow Trout Fry Syndrome (RTFS). To date, diagnosis relies mainly on direct microscopy or cultural methods. Direct microscopy is fast but not very reliable, whereas cultural methods are reliable but time-consuming and labor-intensive. So far fluorescent in situ hybridization (FISH) has not been used in the diagnosis of flavobacteriosis but it has the potential to rapidly and specifically detect F. psychrophilum in infected tissues. Outbreaks in fish farms, caused by pathogenic strains of Flavobacterium species, are increasingly frequent and there is a need for reliable and cost-effective techniques to rapidly diagnose flavobacterioses. This study is aimed at developing a FISH that could be used for the diagnosis of F. psychrophilum infections in fish. We constructed a generic probe for the genus Flavobacterium ("Pan-Flavo") and two specific probes targeting F. psychrophilum based on 16S rRNA gene sequences. We tested their specificity and sensitivity on pure cultures of different Flavobacterium and other aquatic bacterial species. After assessing their sensitivity and specificity, we established their limit of detection and tested the probes on infected fresh tissues (spleen and skin) and on paraffin-embedded tissues. The results showed high sensitivity and specificity of the probes (100% and 91% for the Pan-Flavo probe and 100% and 97% for the F. psychrophilum probe, respectively). FISH was able to detect F. psychrophilum in infected fish tissues, thus the findings from this study indicate this technique is suitable as a fast and reliable method for the detection of Flavobacterium spp. and F. psychrophilum.

Radical chain reactions involving 9-alkyl-9-borafluorenes

The preparation of 9-alkyl-9-borafluorenes and their use as radical precursors in chain reactions were investigated. These organoboranes were found to be excellent precursors of primary and secondary alkyl radicals. Reactions were readily initiated by traces of oxygen and efficient processes involving sulfonyl-based radical traps were discovered. Due to the very high reactivity of the intermediate 9-H and 9-alkyl-9-borafluorenes, problems of reproducibility were identified.