Treatment of pregnant rhesus macaques with testosterone propionate: observations on its fate in the fetus

Castrated male primates, unlike castrated male rodents, respond to exogenous estrogen by releasing gonadotropin. Although this disparity is unexplained, it may occur because the amount of testicular androgen secreted during a critical period for sexual differentiation is not sufficient to completely androgenize the anlagen of the central nervous system (CNS) in male primates. Therefore, male primates might be incompletely masculinized, and if fetal males were exposed to additional androgen during sexual development, they would no longer display the positive feedback to estrogen that usually characterizes females. Besides the development of mechanisms mediating the release of gonadotropins, questions about relationships between adult male sexual behaviors and the intensity of the androgen stimulus upon developing neural structures are of interest. We tested some of these possibilities by injecting androgen into 8 pregnant rhesus macaques from Days 40 through 50 of gestation, and we compared serum levels of testosterone (T), dihydrotestosterone (DHT), and androstenedione (delta 4) in the fetal circulation with that of 5 untreated control males. Fetal sera (both male and female) from treated pregnancies did not contain significantly greater quantities of T and DHT than sera of intact control males from untreated mothers. The maternal sera, however, contained large amounts of T (125.05 +/- 27.40 [SEM] ng/ml, n = 8) and significant elevations of DHT and delta 4 after treatment. The concentrations of delta 4 in the fetal circulation were significantly elevated (p less than 0.01) in treated fetuses compared to intact control males, probably due to the actions of the 17 beta-hydroxysteroid dehydrogenases in the placenta, the fetus, or both.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response characteristics of vibration-sensitive neurons in the midbrain of the grassfrog,Rana temporaria

Summary European grassfrogs (Rana temporaria) were stimulated with pulsed sinusoidal, vertical vibrations (10–300 Hz) and the responses of 46 single midbrain neurons were recorded in awake, immobilized animals.Most units (40) had simple V-shaped excitatory vibrational tuning curves. The distribution of best frequencies (BF's) was bimodal with peaks at 10 and 100 Hz and the thresholds ranged from 0.02 to 1.28cm/s² at the BF.Twenty-three neurons showed phasic-tonic and 11 neurons phasic responses. The dynamic range of seismic intensity for most neurons was 20–30 dB.In contrast to the sharp phase-locking in peripheral vibration-sensitive fibers, no phase-locking to the sinusoidal wave-form was seen in the midbrain neurons. The midbrain cells did not respond at low stimulus intensities (below 0.01–0.02 cm/s²) where a clear synchronization response occurs in saccular fibers.Six midbrain neurons had more complex response characteristics expressed by inhibition of their spontaneous activity by vibration or by bi-and trimodal sensory sensitivities.In conclusion, the vibration sensitive cells in the midbrain of the grassfrog can encode the frequency, intensity, onset and cessation of vibration stimuli. Seismic stimuli probably play a role in communication and detection of predators and the vibration-sensitive midbrain neurons may be involved in the central processing of such behaviorally significant stimuli.Abbreviation BF best frequency     

Lymphangioleiomyomatosis. Is fine needle aspiration cytodiagnosis possible?

Lymphangioleiomyomatosis is a rare condition characterized by a proliferation of the smooth muscle cells, mainly in the lymphatic system, giving rise to blockage of the thoracic duct with chylothorax and chyloascites. This condition was seen in a 34-year-old woman with an abdominal tumor that was subjected to fine needle aspiration. The cytologic diagnosis of this neoplasm is difficult since the cellularity and the cytologic picture indicate malignancy. The organoid configuration together with the chylus formation gave an important clue to the correct diagnosis, which, however, was not made until after a biopsy was performed and the cytologic and histologic findings were combined. The cytologic, histologic and electron microscopic findings are presented.     

Characterization of a native mRNA containing preinitiation complex from rabbit reticulocytes: RNA and protein constituents

From a rabbit reticulocyte postpolysomal supernatant a fraction has been isolated which is enriched in ribosomal particles sedimenting at 50S. This fraction is efficiently in vitro translated predominantly into α-globin. Besides the RNAs and proteins of the small ribosomal subunit the 50S particle contains α-globin mRNA and additional high molecular weight proteins, most of which correspond to polypeptides of the initiation factors eIF-2 and eIF-3. The 50S particle may represent a native [mRNA·40S·eIF′s·Met-tRNA_f·GTP] complex which may occur in vivo as a translatable intermediate in the initiation sequence.     

Associations between Vitamin D Status and Type 2 Diabetes Measures among Inuit in Greenland May Be Affected by Other Factors

ObjectiveEpidemiological studies have provided evidence of an association between vitamin D insufficiency and type 2 diabetes. Vitamin D levels have decreased among Inuit in Greenland, and type 2 diabetes is increasing. We hypothesized that the decline in vitamin D could have contributed to the increase in type 2 diabetes, and therefore investigated associations between serum 25(OH)D3 as a measure of vitamin D status and glucose homeostasis and glucose intolerance in an adult Inuit population.Methods2877 Inuit (≥18 years) randomly selected for participation in the Inuit Health in Transition study were included. Fasting- and 2hour plasma glucose and insulin, C-peptide and HbA_1c were measured, and associations with serum 25(OH)D3 were analysed using linear and logistic regression. A subsample of 330 individuals who also donated a blood sample in 1987, were furthermore included.ResultsAfter adjustment, increasing serum 25(OH)D3 (per 10 nmol/L) was associated with higher fasting plasma glucose (0.02 mmol/L, p = 0.004), 2hour plasma glucose (0.05 nmol/L, p = 0.002) and HbA_1c (0.39%, p<0.001), and with lower beta-cell function (-1.00 mmol/L, p<0.001). Serum 25(OH)D3 was positively associated with impaired fasting glycaemia (OR: 1.08, p = 0.001), but not with IGT or type 2 diabetes.ConclusionsOur results did not support an association between low vitamin D levels and risk of type 2 diabetes. Instead, we found weak positive associations between vitamin D levels and fasting- and 2hour plasma glucose levels, HbA_1c and impaired fasting glycaemia, and a negative association with beta-cell function, underlining the need for determination of the causal relationship.     

Phosphorylation of CD19 Y484 and Y515, and linked activation of phosphatidylinositol 3-kinase, are required for B cell antigen receptor-mediated activation of Bruton's tyrosine kinase

Bruton's tyrosine kinase (Btk) plays a critical role in B cell Ag receptor (BCR) signaling, as indicated by the X-linked immunodeficiency and X-linked agammaglobulinemia phenotypes of mice and men that express mutant forms of the kinase. Although Btk activity can be regulated by Src-family and Syk tyrosine kinases, and perhaps by phosphatidylinositol 3,4,5-trisphosphate, BCR-coupled signaling pathways leading to Btk activation are poorly understood. In view of previous findings that CD19 is involved in BCR-mediated phosphatidylinositol 3-kinase (PI3-K) activation, we assessed its role in Btk activation. Using a CD19 reconstituted myeloma model and CD19 gene-ablated animals we found that BCR-mediated Btk activation and phosphorylation are dependent on the expression of CD19, while BCR-mediated activation of Lyn and Syk is not. Wortmannin preincubation inhibited the BCR-mediated activation and phosphorylation of Btk. Btk activation was not rescued in the myeloma by expression of a CD19 mutant in which tyrosine residues previously shown to mediate CD19 interaction with PI3-K, Y484 and Y515, were changed to phenylalanine. Taken together, the data presented indicate that BCR aggregation-driven CD19 phosphorylation functions to promote Btk activation via recruitment and activation of PI3-K. Resultant phosphatidylinositol 3,4,5-trisphosphate probably functions to localize Btk for subsequent phosphorylation and activation by Src and Syk family kinases.     

A comparison of image and observer based aerial surveys of narwhal

From 25 to 30 August 2014 a double‐observer line‐transect survey was conducted over Melville Bay, home to one of two summering populations of narwhal (Monodon monoceros) off West Greenland. A total of 1,932 linear kilometers was surveyed along 33 transects. In addition to using observers, the aircraft was equipped with two oblique cameras to capture a comparable data set. Analysts reviewed the images for narwhal sightings, which were then matched to the observer sightings. The objectives of the study were to determine advantages and disadvantages of the detection capabilities of both methodologies, and to conduct a comparative analysis of population abundance estimates. Correcting for the truncated detection distance of the images (500 m), the image analysts recorded more sightings (62) and a lower mean group size (2.2) compared to aerial observers (36 and 3.5, respectively), resulting in comparable numbers of individuals detected by both platforms (135 vs. 126). The abundance estimate based on the image sightings was 2,536 (CV = 0.51, 95% CI: 1,003–6,406), which was not significantly different from the aerial observers estimate of 2,596 individuals (CV = 0.51; 95% CI: 961–7,008). This study supports the potential of using UAS for marine mammal abundance studies.     

Leeches as a source of mammalian viral DNA and RNA—a study in medicinal leeches

Surveillance of wild vertebrates can be challenging in remote and inaccessible areas such as tropical rainforests. Blood-feeding parasites, such as leeches, can facilitate wild vertebrate monitoring by targeting residual DNA from the animals the leeches feed on. Successes in detecting host DNA from leeches suggest that host viruses may also be detectable. To systematically test this hypothesis, we performed a proof of concept study using quantitative PCR (qPCR) to detect DNA viruses (bovine herpesvirus [BHV], human adenovirus [HAdV]) and RNA viruses (influenza A [InfA] and measles morbillivirus [MeV]) from nucleic acids extracted from medicinal leeches fed with blood spiked with each virus. All viruses except BHV showed a gradual decline in concentration from day 1 to 50, and all except BHV were detectable in at least half of the samples even after 50 days. BHV exhibited a rapid decline at day 27 and was undetectable at day 50. Our findings in medicinal leeches indicate that leeches collected in the wild might be an untapped resource for detecting vertebrate viruses and could provide new opportunities to study wildlife viral diseases of rare species in challenging environments, where capturing and handling of animals is difficult.