LC–MS method for detecting prostratin in plant extracts and identification of a high-yielding population of Euphorbia fischeriana

Prostratin, a tigliane phorbol ester with promise for the treatment of HIV, was identified and quantified in Euphorbia fischeriana root extracts obtained from several different sites in China. The greatest yield was recovered from root samples collected from Yakeshi, Inner Mongolia (63.54 μg/g dry weight, or 0.00635% by mass). Prostratin was not detected in extracts of Euphorbia sp., E. esula, E. lucorum or Stellera chamaejasme. The presence of prostratin was verified by ¹H and ¹³C NMR. Major fragmentation products were identified from ESI MSⁿ spectra after HPLC separation, providing a reproducible fingerprint for unambiguously recognizing the compound in plant extracts.     

Polygynandry in a red fox population: implications for the evolution of group living in canids?

Canid social groups are typically thought to consist of extendedfamilies, that is, a dominant breeding pair and related nonbreedingsubordinates, that principally obtain indirect fitness benefitsfrom helping to raise the offspring of the dominant pair. Consequently,the monogamous pair has been viewed as the basic fundamentalunit of canid social organization. However, there have beenfew genetic studies that have tested this assumption. We analyzedthe parentage of red foxes (Vulpes vulpes) in a high-density(19.6–27.7 adult foxes/km²) population in Bristol, UK,to determine (1) whether groups typically produced a singlelitter of cubs annually and (2) whether male and female foxesexhibited monogamous mating strategies. Social monogamy (theproduction of one litter in a social group) was observed orassumed in 54% of breeding attempts (N = 13 group-years). However,polyandrous and polygynous patterns of mating were common. Multiplepaternity was confirmed in 38% of litters (N = 16) containingoffspring with resolved maternity and paternity (N = 30 cubs);when including cubs with unresolved paternity (N = 20), multiple-paternitymay have occurred in 69% of litters. Litters were sired by anaverage of 1.6 identified males (range = 1–4); when includingcubs with unresolved paternity, litters may have been siredby up to seven males. Only 20% (6/30) of cubs with resolvedmaternity and paternity were sired by males within the socialgroup. Within groups, dominant females did not breed with subordinatemales; dominant males did breed with subordinate females. Dominantand subordinate females both produced cubs with dominant andsubordinate males from other social groups. Mean adult relatednessin groups typically ranged from 0.15–0.35, indicativeof second-order rather than first-order relatives.     

Oligonucleotide uptake in leukocytes is dependent on extracellular calcium: a hint for the involvement of adhesion molecules?

Abstract

An enhanced appreciation of internalization of antisense oligonucleotides will extend possible applications in experimental and therapeutic settings. We found that oligonucleotide incorporation in monocytes, granulocytes and B-lymphocytes but not in T-lymphocytes is strongly dependent on the presence of extracellular calcium, and is inhibited by heparin. Our results support the hypothesis that calcium-dependent adhesion molecules mediate oligonucleotide internalization in leukocytes.     

Specialized sound reception in dolphins—a hint for the function of the dorsal cochlear nucleus in mammals

Dolphins have developed a specialized system for sound reception. Their pinnae are reduced and shifted under the skin, and sound is transduced via the lower jaw to the auditory ossicles. In line with their auditory functions (notably echolocation), most auditory nuclei in the brain stem of dolphins are extremely well‐developed. In contrast, the dorsal cochlear nucleus is drastically reduced. In the La Plata dolphin the volume of the dorsal cochlear nucleus is 4 mm³, while that of the ventral cochlear nucleus is 98 mm³. The reduction in size of the dorsal cochlear nucleus is also seen in baleen whales, which do not echolocate and are, in contrast to dolphins, tuned to deep frequencies. However, dolphins and baleen whales have the reduction of the outer ear in common. In humans, cats, bats and seals, there is a correlation between the development of pinnae and the dorsal cochlear nucleus. So, we conclude that the function of the dorsal cochlear nucleus in mammals could be to eliminate “auditory artifacts”; arising from the operation of the pinnae.     

Kisspeptide in the estrous mare: Is it an appropriate ovulation-inducing agent?

Kisspeptides (KiSS) are a recently discovered family of neuropeptides with a central role in regulating the onset of reproductive function in all animals studied to date. We have established biological and physiological evidence for KiSS signaling in the mare. The objective of the current study was to evaluate the physiological and behavioral responses of mares repeatedly given the equine-specific kisspeptpin decapeptide (eKp-10, YRWNSFGLRY-NH₂) in an effort to shorten the interovulatory period. Administration of eKp-10 (0.5 mg iv every 4 h) to mares beginning on Day 16 postovulation (Group 2) or in estrus (Group 3) did not shorten the mean ± SEM interovulatory interval compared with untreated (Group 1) controls (21.9 ± 1.2, 22 ± 1.2, and 21.5 ± 1.5 days in Groups 1 to 3, respectively; N = 6 per group), nor was there a significant difference in follicle diameter before ovulation among groups, nor number of days treated with eKp-10 for Groups 2 and 3. Mean daily concentrations of FSH, the preovulatory LH surge (timing, mean, and peak concentrations), and mean progesterone concentrations from the newly formed CL were not significantly different among groups. The initiation of treatment was negatively correlated with sexual receptivity (scored 0 to 5: no interest to strong interest) and serum estradiol concentrations, indicating that eKp-10 can significantly disrupt normal sexual receptivity in the estrous mare. This effect on sexual receptivity was short-lived (< 72 h) and the overall change in sexual receptivity score was not significantly different between Groups 2 and 3 (−1.2 ± 0.5 and −1.4 ± 0.4, respectively). However, the day of the cycle that treatment was initiated significant affected the decline in sexual receptivity score, such that the later in the cycle that treatment was initiated, the greater the estimated decrease in sexual receptivity. In conclusion, the linear hypothalamic-pituitary mechanism for KiSS described in other species was not appropriate for the horse and administration of eKp-10 in the seasonally estrous mare may have been outside of the hormone's normal physiological context.     

Translational control of maturation-protein synthesis in phage MS2: a role for the kinetics of RNA folding?

The gene for the maturation (A) protein of the single-stranded RNA coliphage MS2 is preceded by an untranslated leader of 130 nt. Secondary structure of the leader was deduced by phylogenetic comparison and by probing with enzymes and chemicals. The RNA folds into a cloverleaf, i.e., three stem-loop structures enclosed by a long-distance interaction (LDI). This LDI is essential for translational control. Its 3'moiety contains the Shine-Dalgarno region of the A-protein gene, whereas its complement is located 80 nt upstream, i.e., about 30 nt from the 5'-terminus of the RNA chain. Mutational analysis shows that this base pairing represses expression of the A-protein gene. We present a model in which translational starts can only take place on nonequilibrated RNA, in which base pairing between the complementary regions has not yet taken place. We suggest that this pairing is kinetically delayed by the intervening sequence, which contains the three hairpins of the cloverleaf. The model is mainly based on the observation that reducing the length of the intervening sequence reduces expression, whereas increasing the length has the opposite effect. In addition, further stabilization of the LDI by a stronger base pair does not lead to a decrease in A-protein synthesis. Such a decrease is predicted to occur if translation would be controlled by the equilibrium structure of the leader RNA. These and other observations fit a kinetic model of translational control by RNA folding.     

Body odor evoked potentials: a new method to study the chemosensory perception of self and non‐self in humans

A new method will be presented which allows the perception of body odors in humans to be studied objectively. The analysis of body odor‐evoked potentials was used to investigate if and how the human brain is able to differentiate self from non‐self body odor for the first time. Six subjects (three females) participated in two experimental sessions. In each session, two body odors (axillary hair) were presented within an olfactory oddball paradigm. One of the odors was collected from the subject and the other from an odor donor of the same sex. In the first session the subjects' attention was distracted to a secondary task (passive paradigm), in the second session the subjects were asked to actively differentiate the odors (active paradigm). For the EEG recordings the odors were presented within a constantly flowing airstream. The results show that the subjects could hardly differentiate the body odors subjectively. However, it could be demonstrated that the central nervous processing of one's own odor was faster than the processing of the chemosensory non‐self signal. Moreover, in the active paradigm, the potentials appeared to be larger when the subjects perceived their own body odor. The conclusion is reached that the measurement of chemosensory event‐related potentials (CSERP) is the method of choice for the investigation of HLA‐associated body odors. This revised version was published online in July 2006 with corrections to the Cover Date.     

What is the evidence for the clinical value of SBRT in cancer of the cervix?

AimThe aim of this review is to describe and analyze indications and results of the use of SBRT in uterine cervix cancer, reviewing articles published from January 2010 up to August 2017, for any one of the four indications listed:

• 1Patient refusal or anatomic impediments to interstitial or intracavitary brachytherapy (BCT), i.e. SBRT as an “alternative” for BCT;
• 2Patients with voluminous tumors, or asymmetric tumors where BCT alone would not achieve curative doses, i.e. SBRT as a primary adjunct to BCT;
• 3Pelvic and para aortic adenopathy where SBRT could be used as a boost, i.e. SBRT as a primary adjunct to external beam pelvic radiotherapy;
• 4Small volume recurrences (postoperative or post radiotherapy), i.e. SBRT for salvage.

BackgroundCervix cancer standard treatment involves pelvic irradiation and chemotherapy, recent advances in irradiation techniques might offer new possible approaches.Material and methodsSystematic review of the English language literature about Cervix cancer, SBRT, published from January 2010 to January 2018 identified through a database search of PubMed, and Ovid MEDLINE, using pre-defined search phrases.ResultsThe results in the literature, in general, demonstrate rather weak efficacy of SBRT. In this review, we did not find strong evidence to recommend routine SBRT as a primary treatment for cervico-uterine cancers, i.e. as a replacement for BCT; in highly selected cases it might be considered useful as salvage therapy for relapsed cervix cancer.ConclusionThe existing data to not warrant recommending SBRT for the definitive treatment of cervix cancer, but may have some value in the recurrent/relapsed setting.     

Are BMI and other anthropometric measures appropriate as indices for obesity? A study in an Asian population

We have examined the relationships between percentage of body fat (PBF) and risk factors for cardiovascular disease and insulin resistance and how good body mass index (BMI) and other anthropometric measures are as indices of obesity. High PBF levels were associated with increased risk of cardiovascular disease and insulin resistance. The World Health Organization BMI of 30 kg/m(2) for obesity has low sensitivity, 6.7% and 13.4% for men and women, respectively. For every obese man and woman identified, 6.7 and 1.76 times nonobese men and women, respectively, will be misclassified as obese. With the locally established BMI cutoff point for obesity of 27 kg/m(2) for men and 25 kg/m(2) for women, the sensitivity was improved to 46.7% and 60.8%, respectively. For every obese man and woman identified, 3.76 and 1.64 times nonobese men and women, respectively, will be misclassified as obese. None of the other anthropometric indices was better than the locally established BMIs. We showed that the BMIs for obesity for our local men and women are different. These BMIs were most precise among all indices studied. However, they still lead to high false-positive rates. For more effective management of the problem of obesity, we need to develop more precise, simple, and cost-effective methods for the measurement of PBF.     

Seasonal variation in the population growth rate of a dominant zooplankter: what determines its population dynamics?

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Maturational profiles and migration in the female adolescent population of Madrid: is there a need for a new perspective?

The aim of this study is to assess anthropometric changes and menstrual cycle characteristics during the maturation process of an adolescent female sample in Madrid, Spain. The new demographic context of Madrid, with a 33.9% of girls coming from Central and South America, makes this study relevant in terms of new epidemiological situations that could possible develop. The sample consists of 284 girls, ages 9 to 16 years, measured and interviewed in four school centres of Madrid. Results show that menarche is slightly earlier in the Spanish girls, but there are no other important differences regarding the characteristics of their menses. However, the Spanish girls have a significantly higher intake of menarcheal pain related drugs. The anthropometric changes accompanying menarche are greater in the immigrants, especially in terms of trunk fatness, leading to an "overweight" characterisation of this sub-sample. These maturational profiles show the need for educational programs, especially focussed on the foreign adolescent population, to cope with health risks related to overweight.     

Prognostic value of MIB-1 proliferation index in solitary fibrous tumors of the pleura implemented in a new score – a multicenter study

Background

Although the majority of solitary fibrous tumors of the pleura (SFTP) follow a benign course, 10–25% of patients suffer from recurrence or metastatic disease. Several scoring models have been proposed to predict the outcome. However, none of these included immunohistochemical (IHC) markers as possible prognosticators.

Methods

In this multicenter study, we collected clinical data and formalin-fixed and paraffin-embedded (FFPE) tissue blocks of patients with histologically proven SFTP which had been surgically resected between 2000 und 2015. After systematic and extensive IHC staining on tissue microarrays, the results were analyzed and compared to histomorphological and clinical data for their possible prognostic value.

Results

In total, 78 patients (mean age 61?±?11 years) were included. Of these, 9 patients (11%) had an adverse outcome including SFTP recurrence (n?=?6) or SFTP-related death (n?=?3). Mean overall survival was 172?±?13 months. 1 and 10-year event-free survival rates were 99% and 93%. In the multivariable analysis only MIB-1 proliferation index (Ki-67) ≥10% (HR 12.3, CI 1.1–139.5, p?=?0.043), ≥4 mitoses per 10 high power fields (HR 36.5, CI 1.2–1103.7, p?=?0.039) and tumor size larger than 10 cm (HR 81.8, CI 1.7–4016.8, p?=?0.027) were independently associated with adverse outcome.

Conclusion

A high proliferation rate by MIB-1 IHC was associated with impaired outcome. Upon this, we established a new score using mitosis, necrosis, size of the tumor and MIB-1, which performed better than the traditional scores in our data set. This prognostic score could help to better evaluate outcome of SFTP, but requires external validation.

     

Establishment of a coastal fish in the Azores: recent colonisation or sudden expansion of an ancient relict population?

The processes and timescales associated with ocean-wide changes in the distribution of marine species have intrigued biologists since Darwin''s earliest insights into biogeography. The Azores, a mid-Atlantic volcanic archipelago located >1000 km off the European continental shelf, offers ideal opportunities to investigate phylogeographic colonisation scenarios. The benthopelagic sparid fish known as the common two-banded seabream (Diplodus vulgaris) is now relatively common along the coastline of the Azores archipelago, but was virtually absent before the 1990s. We employed a multiple genetic marker approach to test whether the successful establishment of the Azorean population derives from a recent colonisation from western continental/island populations or from the demographic explosion of an ancient relict population. Results from nuclear and mtDNA sequences show that all Atlantic and Mediterranean populations belong to the same phylogroup, though microsatellite data indicate significant genetic divergence between the Azorean sample and all other locations, as well as among Macaronesian, western Iberian and Mediterranean regions. The results from Approximate Bayesian Computation indicate that D. vulgaris has likely inhabited the Azores for ∼40 (95% confidence interval (CI): 5.5–83.6) to 52 (95% CI: 6.32–89.0) generations, corresponding to roughly 80–150 years, suggesting near-contemporary colonisation, followed by a more recent demographic expansion that could have been facilitated by changing climate conditions. Moreover, the lack of previous records of this species over the past century, together with the absence of lineage separation and the presence of relatively few private alleles, do not exclude the possibility of an even more recent colonisation event.     

Who will desire upper airway stimulation as a treatment of obstructive sleep apnea in the Japanese patient population?

Sleep and Biological Rhythms -