Further characterization of the effects of hypophysectomy, FSH and estrogen on LH stimulation of testosterone production in Leydig cells isolated from immature rats.

Hypophysectomy of immature rats results after 5 days in a loss of LH responsiveness of Leydig cells. LH responsiveness can be partly maintained by treatment with FSH for 5 days. When estradiol benzoate was administered together with FSH to hypophysectomized rats the maintenance of LH responsiveness was not observed. The loss in LH responsiveness after hypophysectomy in terms of testosterone production could not be explained by either a change in the amount of Leydig cells present in the Leydig cell preparation or to a higher conversion of testosterone. The LH-stimulated cAMP production in cells from hypophysectomized rats was very low compared to cells from intact rats. There was no difference between cAMP production of Leydig cells from untreated, FSH-treated or FSH plus estradiol benzoate treated hypophysectomized rats. During the first 2 days after hypophysectomy LH responsiveness in both untreated and FSH-treated rats showed a comparable decrease. From day 2 after hypophysectomy LH responsiveness remained at a constant level in cells from rats treated with FSH, but declined further in cells from untreated rats. A single injection of estradiol benzoate to hypophysectomized rats treated with FSH counteracted the effect of FSH on LH responsiveness, but only when estradiol was administered at that time after hypophysectomy, when the effect of FSH on LH responsiveness was clear.     

Proteome Analysis Database: online application of InterPro and CluSTr for the functional classification of proteins in whole genomes

The SWISS-PROT group at EBI has developed the Proteome Analysis Database utilising existing resources and providing comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archaea and eukaryotes (http://www.ebi.ac. uk/proteome/). The two main projects used, InterPro and CluSTr, give a new perspective on families, domains and sites and cover 31-67% (InterPro statistics) of the proteins from each of the complete genomes. CluSTr covers the three complete eukaryotic genomes and the incomplete human genome data. The Proteome Analysis Database is accompanied by a program that has been designed to carry out InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.     

Dengue Virus Co-opts UBR4 to Degrade STAT2 and Antagonize Type I Interferon Signaling

An estimated 50 million dengue virus (DENV) infections occur annually and more than forty percent of the human population is currently at risk of developing dengue fever (DF) or dengue hemorrhagic fever (DHF). Despite the prevalence and potential severity of DF and DHF, there are no approved vaccines or antiviral therapeutics available. An improved understanding of DENV immune evasion is pivotal for the rational development of anti-DENV therapeutics. Antagonism of type I interferon (IFN-I) signaling is a crucial mechanism of DENV immune evasion. DENV NS5 protein inhibits IFN-I signaling by mediating proteasome-dependent STAT2 degradation. Only proteolytically-processed NS5 can efficiently mediate STAT2 degradation, though both unprocessed and processed NS5 bind STAT2. Here we identify UBR4, a 600-kDa member of the N-recognin family, as an interacting partner of DENV NS5 that preferentially binds to processed NS5. Our results also demonstrate that DENV NS5 bridges STAT2 and UBR4. Furthermore, we show that UBR4 promotes DENV-mediated STAT2 degradation, and most importantly, that UBR4 is necessary for efficient viral replication in IFN-I competent cells. Our data underscore the importance of NS5-mediated STAT2 degradation in DENV replication and identify UBR4 as a host protein that is specifically exploited by DENV to inhibit IFN-I signaling via STAT2 degradation.     

Wealth transmission and inequality among hunter-gatherers

We report quantitative estimates of intergenerational transmission and population-wide inequality for wealth measures in a set of hunter-gatherer populations. Wealth is defined broadly as factors that contribute to individual or household well-being, ranging from embodied forms such as weight and hunting success to material forms such household goods, as well as relational wealth in exchange partners. Intergenerational wealth transmission is low to moderate in these populations, but is still expected to have measurable influence on an individual's life chances. Wealth inequality (measured with Gini coefficients) is moderate for most wealth types, matching what qualitative ethnographic research has generally indicated (if not the stereotype of hunter-gatherers as extreme egalitarians). We discuss some plausible mechanisms for these patterns, and suggest ways in which future research could resolve questions about the role of wealth in hunter-gatherer social and economic life.     

Comparison of quasisteady-state performance of the DEAMOX process under intermittent and continuous feeding and different nitrogen loading rates

The recently developed denitrifying ammonium oxidation (DEAMOX) process combines the anammox reaction with autotrophic denitrifying conditions using sulfide as an electron donor for the production of nitrite from nitrate within an anaerobic biofilm. This paper compares a quasisteady-state performance of this process for treatment of baker's yeast wastewater under intermittent and continuous feeding and increasing nitrogen loading rate (NLR) from 300 till 858 mg N/L/d. The average total nitrogen removal slightly decreased on increasing the NLR: from 86 to 79% (intermittent feeding) and from 87 to 84% (continuous feeding). The better performance under continuous feeding was due to a more complete nitrate removal in the former case whereas the ammonia removal was similar for both feeding regimes under the comparable NLR. A possible explanation can be that, during continuous feeding (simultaneous supply of nitrate and sulfide), there were less mass transfer limitations for sulfide oxidizing denitrifiers presumably located in the outer layer of sludge aggregates. On the contrary, the ammonia oxidisers presumably located inside the aggregates apparently suffered from nitrite mass transfer limitations under both the feedings. The paper further describes some characteristics of the DEAMOX sludge.     

Continuous fetal heart rate monitoring during late gestation in cattle by means of Doppler ultrasonography: reference values obtained by computer-assisted analysis

Continuous fetal heart rate (FHR) monitoring using transabdominal Doppler ultrasonography can be assumed to provide information about the viability of the bovine fetus during late gestation, as has been found in humans. To be able to recognize unfavourable fetal conditions, first the normal ranges of FHR parameters in cattle should be established. Therefore, in this study we aimed to determine the normal ranges of computerized FHR parameters, like basal fetal heart rate (BHR), number of accelerations and decelerations per hour and short and long term variation (STV and LTV) during the last 3 weeks before calving (n = 21 cows). Each cow had one recording in each of three episodes of 7 days before parturition. As recording time in the cow is limited, we also studied whether these FHR parameters differ between recordings of 30 and 60 min duration (n = 31 pairs of recordings). The outcomes of FHR recordings with a duration of 30 or 60 min did not differ significantly, except for a higher percentage of signal loss in the 60 min recordings. Therefore, determination of normal ranges was performed in 30 min recordings. BHR decreased from 3 to 2 weeks (114 to 109 bpm; P < 0.0001) before parturition and then remained constant until 2 days before calving. The mean number of accelerations per hour ranged between 4.4 and 5.0 h(-1) and did not change significantly with time. Compared to 3 weeks before parturition, STV was significantly higher at 2 weeks (P < 0.05), but not at 1 week before parturition (8.1, 10.0, and 9.2 ms, respectively). Changes in LTV showed a time course comparable to that of STV, but significance was not reached (51.4, 58.6, and 58.4 ms for respectively 3, 2 and 1 weeks before parturition). No decelerations were found during the period understudy. In conclusion, this study has provided normal ranges of bovine computerized FHR parameters during the last 3 weeks of gestation, allowing a comparison with data from cows with compromised gestations in future.     

Myocardial Revascularization in High-Risk Coronary Patients

It is recognized that postoperative mortality, infarction and the need for inotropic support are increased following myocardial revascularization in highrisk patients. Operations were carried out in 57 such patients in whom one or more of the following factors were present: ventricular dysfunction—ejection fraction less than 0.4 (17), unstable (8) or preinfarction angina (29), evolving infarction (8), recent infarction (less than two weeks before) (5) and refractory ventricular tachyarrhythmia (4). Combined risk factors were present in nine patients. The following principles were utilized to minimize ischemic injury: (1) avoidance of prebypass hypertension and hypotension, (2) avoidance of extreme hemodilution, (3) avoidance of ventricular fibrillation, (4) maintenance of beating empty heart, when possible, (5) the limiting of ischemic periods to less than 12 minutes (hypothermia 32°C) and (6) repaying myocardial oxygen debt with total (vented) bypass, when necessary. The following results were obtained: inotropic support was required in five patients (9 percent), “new” postoperative infarction occurred in five patients (9 percent) and one patient died (2 percent). These results are comparable to those reported in good-risk patients, and indicate that optimal myocardial protection will allow safe revascularization in a high-risk patient.     

Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists

This Letter describes the synthesis and SAR, developed through an iterative analogue library approach, of a novel series of selective M1 mAChR antagonists for the potential treatment of Parkinson's disease, dystonia and other movement disorders. Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5.     

Principles of Rodent Surgery for the New Surgeon

For both scientific and animal welfare reasons, training in basic surgical concepts and techniques should be undertaken before ever seeking to perform surgery on a rodent. Students, post-doctoral scholars, and others interested in performing surgery on rodents as part of a research protocol may not have had formal surgical training as part of their required coursework. Surgery itself is a technical skill, and one that will improve with practice. The principles of aseptic technique, however, often remain unexplained or untaught. For most new surgeons, this vital information is presented in piecemeal fashion or learned on the job, neither of which is ideal. It may also make learning how to perform a particular surgery difficult, as the new surgeon is learning both a surgical technique and the principles of asepsis at the same time. This article summarizes and makes recommendations for basic surgical skills and techniques necessary for successful rodent surgery. This article is designed to supplement hands-on training by the user''s institution.