Continental scale analysis of bird migration timing: influences of climate and life history traits—a generalized mixture model clustering and discriminant approach

There is substantial evidence of climate-related shifts to the timing of avian migration. Although spring arrival has generally advanced, variable species responses and geographical biases in data collection make it difficult to generalise patterns. We advance previous studies by using novel multivariate statistical techniques to explore complex relationships between phenological trends, climate indices and species traits. Using 145 datasets for 52 bird species, we assess trends in first arrival date (FAD), last departure date (LDD) and timing of peak abundance at multiple Australian locations. Strong seasonal patterns were found, i.e. spring phenological events were more likely to significantly advance, while significant advances and delays occurred in other seasons. However, across all significant trends, the magnitude of delays exceeded that of advances, particularly for FAD (+22.3 and ?9.6 days/decade, respectively). Geographic variations were found, with greater advances in FAD and LDD, in south-eastern Australia than in the north and west. We identified four species clusters that differed with respect to species traits and climate drivers. Species within bird clusters responded in similar ways to local climate variables, particularly the number of raindays and rainfall. The strength of phenological trends was more strongly related to local climate variables than to broad-scale drivers (Southern Oscillation Index), highlighting the importance of precipitation as a driver of movement in Australian birds.     

Merging theory and mechanism in studies of gynodioecy

In gynodioecious species, females and hermaphrodites coexist and the genetics of sex determination is usually nuclear cytoplasmic. Maintaining nuclear-cytoplasmic gynodioecy requires polymorphism for the feminizing genes (contained in the mitochondria) and the genes that restore male fertility (contained in the nucleus). This complex polymorphism depends, in part, on there being negative pleiotropic effects (i.e. costs) of the nuclear restorer alleles. Here, we combine information from theoretical studies and studies on the molecular action of restorer alleles in crops to interpret the probable costs of such alleles, and suggest how various aspects of the theoretical models could be tested. In doing so, we highlight how crops can be used to address evolutionary questions about the maintenance of nuclear-cytoplasmic gynodioecy.     

Evidence for persistent, occult infection in neonatal macaques following perinatal transmission of simian-human immunodeficiency virus SF162P3

To model human immunodeficiency virus (HIV) perinatal transmission, we studied infection of simian-human immunodeficiency virus (SHIV) SF162P3 in 10 pregnant Macaca nemestrina females and their offspring. Four of nine infants born to and suckled by these dams had evidence of infection, a transmission rate of 44.4% (95% confidence interval, 13.7% to 78.8%). We quantified transplacentally acquired and de novo Env-specific immunoglobulin G (IgG), IgM, and neutralizing antibodies in newborns. Transmission of escape variants was confirmed. In utero infection (n = 1) resulted in high viremia, depletion of peripheral CD4+ T cells, and rapid evolution of env in blood and tissues. Peripartum or postpartum SHIV infection (n = 3) resulted in postacute viral control that was undetectable by very sensitive multiplex PCR, despite increasing antibodies. Seropositive infants with highly controlled viremia had homogeneous peripheral blood env sequences, and their tissues had <3 copies per million cells. A high incidence of seropositive virus-low or -negative SHIV infection in infant macaques has implications for HIV type 1 perinatal transmission and detection.     

Tissue strain amplification at the osteocyte lacuna: a microstructural finite element analysis

A parametric finite element model of an osteocyte lacuna was developed to predict the microstructural response of the lacuna to imposed macroscopic strains. The model is composed of an osteocyte lacuna, a region of perilacunar tissue, canaliculi, and the surrounding bone tissue. A total of 45 different simulations were modeled with varying canalicular diameters, perilacunar tissue material moduli, and perilacunar tissue thicknesses. Maximum strain increased with a decrease in perilacunar tissue modulus and decreased with an increase in perilacunar tissue modulus, regardless of the thickness of the perilacunar region. An increase in the predicted maximum strain was observed with an increase in canalicular diameter from 0.362 to 0.421 microm. In response to the macroscopic application of strain, canalicular diameters increased 0.8% to over 1.0% depending on the perilacunar tissue modulus. Strain magnification factors of over 3 were predicted. However, varying the size of the perilacunar tissue region had no effect on the predicted perilacunar tissue strain. These results indicate that the application of average macroscopic strains similar to strain levels measured in vivo can result in significantly greater perilacunar tissue strains and canaliculi deformations. A decrease in the perilacunar tissue modulus amplifies the perilacunar tissue strain and canaliculi deformation while an increase in the local perilacunar tissue modulus attenuates this effect.     

Intraventricular (i3vt) ghrelin increases food intake in fatty Zucker rats

Ghrelin is an orexigenic peptide secreted from the stomach and also made in the brain. Ghrelin receptors are expressed on hypothalamic cells important in appetite and energy balance. We determined that intra-3rd-ventricular (i3vt) ghrelin dose-dependently increases acute (1 and 2 h) food intake in lean and fatty Zucker rats (0, 0.01, 0.1 and 1.0 nmol ghrelin). The percentage increase of food intake in fatty Zucker rats was significantly greater than that in lean rats. Fatty Zucker rats had 4.5 times more ghrelin receptor mRNA in the hypothalamus than lean Zucker rats, suggesting a possible mechanism for the increased sensitivity.     

Cellular Models of Aggregation-dependent Template-directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer Disease

Alzheimer disease (AD) is a degenerative tauopathy characterized by aggregation of Tau protein through the repeat domain to form intraneuronal paired helical filaments (PHFs). We report two cell models in which we control the inherent toxicity of the core Tau fragment. These models demonstrate the properties of prion-like recruitment of full-length Tau into an aggregation pathway in which template-directed, endogenous truncation propagates aggregation through the core Tau binding domain. We use these in combination with dissolution of native PHFs to quantify the activity of Tau aggregation inhibitors (TAIs). We report the synthesis of novel stable crystalline leucomethylthioninium salts (LMTX®), which overcome the pharmacokinetic limitations of methylthioninium chloride. LMTX®, as either a dihydromesylate or a dihydrobromide salt, retains TAI activity in vitro and disrupts PHFs isolated from AD brain tissues at 0.16 μm. The K_i value for intracellular TAI activity, which we have been able to determine for the first time, is 0.12 μm. These values are close to the steady state trough brain concentration of methylthioninium ion (0.18 μm) that is required to arrest progression of AD on clinical and imaging end points and the minimum brain concentration (0.13 μm) required to reverse behavioral deficits and pathology in Tau transgenic mice.