Nonparametric tests for two-group comparisons of dependent observations obtained at varying time points

We propose new tests for two-group comparisons of repeated measures of a response where the repeated measures might be obtained at arbitrary time points that differ over individuals. The tests are almost U-statistics in that the kernel contains some unknown parameters that need to be estimated from the data. Our methods are designed for settings in which response means of one group are strictly greater than the response means of the other group. The tests do not make any assumptions regarding the distribution of the repeated measures except that one of the tests assumes that the repeated measures can be grouped into distinct periods of observations (e.g., around fixed follow-up time points) such that the covariance between scores only depends on the periods the observations belong to and that the covariance matrices are the same in the two groups. The tests are valid even if the probability that a response is observed depends on the level of response provided that the missing data mechanism is the same in both groups. Inference can conveniently be based on resampling. We provide asymptotic results for the test statistics. We investigate size and power of the tests and use them to assess differences in viral load decline for drug-resistant and drug-sensitive human immunodeficiency virus (HIV)-1 infected patients.     

Tryptathionine bridges in peptide synthesis

The tryptathionine linkage is a crosslink formed between tryptophan and cysteine. This feature is characteristic of the bicyclic peptides: the phallotoxins and the amatoxins. These peptides both bind to protein folds of their respective targets (F-actin and RNA pol II, respectively) with extremely high affinities. Studies on these peptides have shown that the tryptathionine crosslink is essential for this binding affinity. Tryptathionines have been investigated for many years and several syntheses exist for their formation. In this review, we report on the various methodologies employed in tryptathionine synthesis, and discuss some of the advantages and disadvantages associated with each of them.     

Assessment of dynamic changes in cerebral autoregulation.

Cerebral autoregulation (CA) is a control mechanism that adjusts cerebral vasomotor tone in response to changes in arterial blood pressure (ABP) to ensure a nearly constant cerebral blood flow. Patient treatment could be optimized if CA monitoring were possible. Whereas the concept of static CA assessment is simply based on comparison of mean values obtained from two stationary states (e.g., before and after a pressure change), the evaluation of dynamic CA is more complex. Among other methods, moving cross-correlation analysis of slow waves in ABP and cerebral blood flow velocity (CBFV) seems to be appropriate to monitor CA quasi-continuously. The calculation of an "instantaneous transfer function" between ABP and CBFV oscillations in the low-frequency band using the Wigner-Ville distribution may represent an acceptable compromise in time-frequency resolution for continuous CA monitoring.     

Functional analysis of a beta-1,6-glucanase gene from the grass endophytic fungus Epichloë festucae

β-1,6-glucanases degrade the polysaccharide β-1,6-glucan, a cell wall component in some filamentous fungi. A single copy of a β-1,6-glucanase gene, designated gcnA, was identified in each of the grass endophytic fungi Neotyphodium lolii and Epichloë festucae. Phylogenetic analysis indicates that the GcnA protein is a member of glycosyl hydrolase family 5, and is closely related to fungal β-1,6-glucanases implicated in mycoparasitism. The E. festucae gcnA gene was expressed in mycelium grown in culture and in both vegetative and reproductive tissues of perennial ryegrass. A gcnA replacement mutant had reduced β-1,6-glucanase activity when grown in media containing pustulan as the major carbon source. β-1,6-glucanase activity was restored in the replacement mutant by introducing multiple copies of the gcnA gene. Growth of ΔgcnA and gcnA-overexpressing strains in vegetative grass tissues was indistinguishable from wild type strains.     

Food supply effects on the asexual reproduction and respiratory metabolism of Aurelia aurita polyps

Hydrobiologia - Ecological speciation, which relies heavily on selection driving the emergence of new species, has become the primary paradigm through which rapid species radiations are understood....     

The Nucleotide‐Dependent Interactome of Rice Heterotrimeric G‐Protein α ‐Subunit

The rice heterotrimeric G‐protein complex, a guanine‐nucleotide‐dependent on‐off switch, mediates vital cellular processes and responses to biotic and abiotic stress. Exchange of bound GDP (resting state) for GTP (active state) is spontaneous in plants including rice and thus there is no need for promoting guanine nucleotide exchange in vivo as a mechanism for regulating the active state of signaling as it is well known for animal G signaling. As such, a master regulator controlling the G‐protein activation state is unknown in plants. Therefore, an ab initio approach is taken to discover candidate regulators. The rice Gα subunit (RGA1) is used as bait to screen for nucleotide‐dependent protein partners. A total of 264 proteins are identified by tandem mass spectrometry of which 32 were specific to the GDP‐bound inactive state and 22 specific to the transition state. Approximately, 10% are validated as previously identified G‐protein interactors.     

No evidence of handling‐induced mortality in Serengeti's African wild dog population

The disappearance of an endangered African wild dog population from Serengeti National Park (SNP) led to international debate centered around one question: were researchers to blame? The “Burrows' hypothesis” postulated that stress induced by research‐related immobilization and handling reactivated a latent rabies virus, eliminating the population. Insufficient data inhibited hypothesis testing, but since wild dogs persisted alongside SNP and have been studied since 2005, the hypothesis can be tested 25 years after its proposition. To be supported, wild dog immobilization interventions should have resulted in high mortality rates. However, 87.6% of 121 handled wild dogs (2006–2016) survived >12 months post‐handling. Some argued that viral reactivation would necessitate long‐term stress. Following immobilization, 67 animals were captured, transported, and held in a translocation enclosure. Despite the longer‐term stress, 95.5% survived >12 months. Furthermore, the stable number of wild dog packs in the ecosystem over the past decade, and lack of recolonization of SNP, strongly oppose Burrows' hypothesis. Instead, factors such as heightened levels of interspecific competition are likely to have contributed to the wild dog disappearance and subsequent avoidance of the Serengeti plains. Handling and radio telemetry are invaluable when studying elusive endangered species, yielding information pertinent to their conservation and management, and had no effect on Serengeti wild dog survival.     

High Phosphohistone H3 Expression Correlates with Adverse Clinical,Biological, and Pathological Factors in Neuroblastomas

Phosphohistone H3 (pHH3), a biomarker of the late G2- and M-phase of the cell cycle, provides a powerful indication of the proliferative state of many cancers. We investigated the prognostic significance of pHH3 by immunostaining 80 neuroblastomas and counting the average number of strongly stained nuclei and mitotic figures. The median and 75th percentile pHH3 proliferation indices (PIs) were 0.54% and 1.06% (range, 0.01% to 2.23%) respectively. pHH3 expression was significantly higher in neuroblastomas from patients with adverse clinical characteristics, all unfavorable pathological factors including high mitosis karyorrhexis index (MKI), and adverse biological factors including MYCN oncogene amplification. High pHH3-PIs, at 1% threshold, were significantly associated with a shorter overall survival (OS) and event-free survival (EFS) in the univariable Cox regression analyses. In the multivariable models, high pHH3 counts were significantly associated with worse OS after adjustment for age but were not independent of either high MKI or MYCN amplification. In children less than 18 months of age, high MKIs and high PHH3-PIs were associated with significantly worse OS and EFS. In conclusion, high pHH3 expression correlates strongly with high MKI and MYCN amplification and indicates poor prognosis in neuroblastomas.