Netrin signaling breaks the equivalence between two identified zebrafish motoneurons revealing a new role of intermediate targets

Background

We previously showed that equivalence between two identified zebrafish motoneurons is broken by interactions with identified muscle fibers that act as an intermediate target for the axons of these motoneurons. Here we investigate the molecular basis of the signaling interaction between the intermediate target and the motoneurons.

Principal Findings

We provide evidence that Netrin 1a is an intermediate target-derived signal that causes two equivalent motoneurons to adopt distinct fates. We show that although these two motoneurons express the same Netrin receptors, their axons respond differently to Netrin 1a encountered at the intermediate target. Furthermore, we demonstrate that when Netrin 1a is knocked down, more distal intermediate targets that express other Netrins can also function to break equivalence between these motoneurons.

Significance

Our results suggest a new role for intermediate targets in breaking neuronal equivalence. The data we present reveal that signals encountered during axon pathfinding can cause equivalent neurons to adopt distinct fates. Such signals may be key in diversifying a neuronal population and leading to correct circuit formation.     

Dating of divergences within the Rattus genus phylogeny using whole mitochondrial genomes

The timing and order of divergences within the genus Rattus have, to date, been quite speculative. In order to address these important issues we sequenced six new whole mitochondrial genomes from wild-caught specimens from four species, Rattus exulans, Rattus praetor, Rattus rattus and Rattus tanezumi. The only rat whole mitochondrial genomes available previously were all from Rattus norvegicus specimens. Our phylogenetic and dating analyses place the deepest divergence within Rattus at approximately 3.5 million years ago (Mya). This divergence separates the New Guinean endemic R. praetor lineage from the Asian lineages. Within the Asian/Island Southeast Asian clade R. norvegicus diverged earliest at approximately 2.9Mya. R. exulans and the ancestor of the sister species R. rattus and R. tanezumi subsequently diverged at approximately 2.2Mya, with R. rattus and R. tanezumi separating as recently as approximately 0.4Mya. Our results give both a better resolved species divergence order and diversification dates within Rattus than previous studies.     

Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.     

Behavior and Welfare of Domestic Cats Housed in Cages Larger than U.S. Norm

The effect of providing additional floor space on cat behavior and welfare is not well documented. This study involved replication of an investigation of cats’ responses to enhanced cage and room environments using cages of 0.56 m² with the same methodology but an increased space allowance of 1.1 m². Singly housed adult cats (n = 59) were randomly assigned to a treatment group that was a combination of a managed or unmanaged room and an enriched or unenriched cage environment. Cats were observed for 2 days for maintenance, affiliative, and avoidant behaviors using scan sampling and 5-min, continuous focal sampling. At the end of Day 2, cats’ reactions to the approach of an unfamiliar person were assessed. Cats housed in enriched/managed environments exhibited more maintenance and affiliative behaviors and fewer avoidant behaviors than cats in unmanaged/unenriched environments, suggesting that macro and micro environments may be equally relevant to the cat. Increased space did not enhance the cats’ welfare outcomes, suggesting that the provision of additional cage space may not be as important to the cat as a managed housing environment.     

Estimating striae of Retzius periodicity nondestructively using partial counts of perikymata

Accurate age estimations for enamel formation and the timing of enamel hypoplasia have traditionally only been available through histological analyses of dental thin sections, which is a difficult and destructive process. However, an association between striae of Retzius periodicity, crucial for accurate aging, and the total number of striae in imbricational enamel has been reported in the literature. This means periodicity can be estimated nondestructively but is reliant on all perikymata being visible along the crown surface. Therefore, crowns with worn or damaged surfaces may not be able to be assessed, potentially limiting sample sizes. We tested this relationship in a modern New Zealand sample and investigated whether reliable associations might be identified using only partial perikymata counts from the cervical half of the crown. Using mandibular canines (n = 11), the distribution of perikymata per decile was recorded using high definition replica surfaces. Thin sections of the same crowns were used to assess periodicity histologically along with striae of Retzius distributions. A strong correlation between total striae numbers and periodicity was also identified in our sample. Furthermore, we report strong correlations that allow periodicity to be estimated from perikymata counts using only 10% of crown height when certain deciles are used. Based on these findings, we propose a simple matrix that can be developed for nondestructively estimating periodicity based on the range of perikymata counts in the sixth to ninth deciles. Am J Phys Anthropol 154:251–258, 2014. © 2014 Wiley Periodicals, Inc.