Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening

Background

In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.

Methods

Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M₁/M₀ and M₂/M₀, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping.

Results

Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M₂/M₀ but not LCI or M₁/M₀. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes.

Conclusion

These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.     

Degree of landscape fragmentation influences genetic isolation among populations of a gliding mammal

Forests and woodlands are under continuing pressure from urban and agricultural development. Tree-dependent mammals that rarely venture to the ground are likely to be highly sensitive to forest fragmentation. The Australian squirrel glider (Petaurus norfolcensis) provides an excellent case study to examine genetic (functional) connectivity among populations. It has an extensive range that occurs in a wide band along the east coast. However, its forest and woodland habitat has become greatly reduced in area and is severely fragmented within the southern inland part of the species' range, where it is recognised as threatened. Within central and northern coastal regions, habitat is much more intact and we thus hypothesise that genetic connectivity will be greater in this region than in the south. To test this we employed microsatellite analysis in a molecular population biology approach. Most sampling locations in the highly modified south showed signatures of genetic isolation. In contrast, a high level of genetic connectivity was inferred among most sampled populations in the more intact habitat of the coastal region, with samples collected 1400 km apart having similar genetic cluster membership. Nonetheless, some coastal populations associated with urbanisation and agriculture are genetically isolated, suggesting the historic pattern observed in the south is emerging on the coast. Our study demonstrates that massive landscape changes following European settlement have had substantial impacts on levels of connectivity among squirrel glider populations, as predicted on the basis of the species' ecology. This suggests that landscape planning and management in the south should be focused on restoring habitat connectivity where feasible, while along the coast, existing habitat connectivity must be maintained and recent losses restored. Molecular population biology approaches provide a ready means for identifying fragmentation effects on a species at multiple scales. Such studies are required to examine the generality of our findings for other tree-dependent species.     

Acetylation of nuclear hormone receptor superfamily members: thyroid hormone causes acetylation of its own receptor by a mitogen-activated protein kinase-dependent mechanism

Because the androgen and estrogen nuclear hormone receptors are subject to acetylation, we speculated that the nuclear thyroid hormone receptor-beta1 (TRbeta1), another superfamily member, was also subject to this posttranslational modification. Treatment of 293T cells that contain TRbeta1(wt) with l-thyroxine (T4)(10(-7)M, total concentration) resulted in the accumulation of acetylated TR in nuclear fractions at 30-45 min and a decrease in signal by 60 min. A similar time course characterized recruitment by TR of p300, a coactivator protein with intrinsic transacetylase activity. Recruitment by the receptor of SRC-1, a TR coactivator that also acetylates nucleoproteins, was also demonstrated. Inhibition of the MAPK (ERK1/2) signal transduction cascade by PD 98059 blocked the acetylation of TR caused by T4. Tetraiodothyroacetic acid (tetrac) decreased T4-induced acetylation of TR. At 10(-7)M, 3,5,3'-triiodo-l-thyronine (T3) was comparably effective to T4 in causing acetylation of TR. We studied acetylation in TR that contained mutations in the DNA-binding domain (DBD) (residues 128-142) that are known to be relevant to recruitment of coactivators and to include the MAPK docking site. In response to T4 treatment, the K128A TR mutant transfected into CV-1 cells recruited p300, but not SRC-1, and was subject to acetylation. R132A complexed with SRC-1, but not p300; it was acetylated equally well in both the absence and presence of T4. S142E was acetylated in the absence and presence of T4 and bound SRC-1 under both conditions; this mutant was also capable of binding p300 in the presence of T4. There was no serine phosphorylation of TR in any of these mutants. We conclude that (1) TRbeta1, like AR and ER, is subject to acetylation; (2) the process of acetylation of TR requires thyroid hormone-directed MAPK activity, but not serine phosphorylation of TR by MAPK, suggesting that the contribution of MAPK is upstream in the activation of the acetylase; (3) the amino acid residue 128-142 region of the DBD of TR is important to thyroid hormone-associated recruitment of p300 and SRC-1; (4) acetylation of TR DBD mutants that is directed by T4 appears to be associated with recruitment of p300.     

Brain, spine, and muscle cytochrome Cu-A redox patterns of change during hypothermic circulatory arrest in swine

Past near infrared spectroscopy (NIRS) studies have reported different changes in cytochrome C oxidase (Cyt) redox status during similar interventions that cause tissue ischaemia. We investigated whether there were distinctive differences when NIRS signals were obtained simultaneously from different tissues during total circulatory arrest. Forty-two healthy 10 kg commercial swine (Sus scrofa) on cardiopulmonary bypass, each underwent 2 to 8 sequential periods of hypothermic circulatory arrest for 7.5 min. Prior to each arrest, key physiologic variables were adjusted to 1 of 81 combinations of high, normal, or low levels of core temperature, hematocrit, pH, and serum glucose. Each combination was repeated at least twice. Simultaneous NIRS monitoring yielded 202 brain, 191 spine, and 199 muscle Cyt data sets, which were then classified into 13 distinctive patterns of change. The data sets always differed between tissues in the same arrest trial and subject. Typically, brain Cyt rapidly became more reduced at the start of arrest and changed little thereafter, muscle Cyt behaved comparably to brain Cyt but continued to become reduced throughout the arrest, and spine Cyt either did not change status or gradually became more reduced over the course of arrest. The spine pattern's mean rate of change was 12 times slower than those of the brain or muscle. The Cyt patterns of change were classified into 13 groups which were significantly related to core temperature in the brain and spine, and hematocrit in muscle. The respiratory response in mitochondria during systemic circulatory arrest differs between brain, spine and muscle tissues in the same subject.     

Human dorsal and ventral auditory streams subserve rehearsal-based and echoic processes during verbal working memory

To hear a sequence of words and repeat them requires sensory-motor processing and something more-temporary storage. We investigated neural mechanisms of verbal memory by using fMRI and a task designed to tease apart perceptually based ("echoic") memory from phonological-articulatory memory. Sets of two- or three-word pairs were presented bimodally, followed by a cue indicating from which modality (auditory or visual) items were to be retrieved and rehearsed over a delay. Although delay-period activation in the planum temporale (PT) was insensible to the source modality and showed sustained delay-period activity, the superior temporal gyrus (STG) activated more vigorously when the retrieved items had arrived to the auditory modality and showed transient delay-period activity. Functional connectivity analysis revealed two topographically distinct fronto-temporal circuits, with STG co-activating more strongly with ventrolateral prefrontal cortex and PT co-activating more strongly with dorsolateral prefrontal cortex. These argue for separate contributions of ventral and dorsal auditory streams in verbal working memory.     

Influence of soil compaction on tunnel network construction by the eastern subterranean termite (Isoptera: Rhinotermitidae)

Eastern subterranean termites, Reticulitermes flavipes (Kollar), workers were introduced into arenas containing low, moderate, and high compaction builder's sand (1.05 g/cm3, 1.18 g/cm3 or 1.35 g/cm3 bulk densities, respectively), and they immediately began tunneling. Termites built the tunnel network significantly fastest in soil of low compaction compared with moderately or highly compacted soil. In soil of low compaction, 221.67 +/- 4.73 cm of total tunnel distance was constructed in 1 d compared with only 96 cm of tunneling in highly compacted soil. At 14 d, total tunnel distance averaged 216.83 +/- 4.56 cm in soil of low compaction compared with 169.70 +/- 4.10 and 181.18 +/- 6.13 cm in moderately and highly compacted soil, respectively. Decreases in total tunnel distance between 1 and 14 d were caused by backfilling of seldom-used tunnels. Termites did the majority of tunneling during the first day of introduction into arenas. In soil of low and moderate compaction, termites essentially constructed the entire tunnel network within the first day, only modifying it by backfilling or maintaining tunnels. In highly compacted soil, 53% of the final tunnel network was constructed during the first day, 87% was constructed by the third day, and 97% was constructed by the seventh day. Soil compaction did not affect the number of primary tunnels or the number and diameter of secondary tunnels. The angle between the secondary tunnel and primary tunnel also was not significantly affected by soil compaction. However, the number of secondary tunnels in soil of low compaction (5.89 +/- 0.51) was significantly greater than in moderately (2.74 +/- 0.36) and highly (3.58 +/- 0.59) compacted soils.     

Eating in the Absence of Hunger: A Genetic Marker for Childhood Obesity in Prepubertal Boys?

Objective: Eating in the absence of hunger (EAH) may be a behavioral trait through which obesity‐promoting genes promote positive energy balance. The primary aim of this study was to compare children born at high vs. low risk for obesity with respect to EAH at 5 years of age. Research Methods and Procedures: This was an observational investigation of families enrolled in the University of Pennsylvania and The Children's Hospital of Philadelphia's Infant Growth Study. Five‐year‐old children born at high (N = 28) or low (N = 25) risk for obesity on the basis of maternal prepregnancy body weight were evaluated at a hospital‐based laboratory. Children consumed 11 snack foods ad libitum after consuming an ad libitum dinner and reporting fullness. Parents reported on snack foods at home and their own eating styles. Nutritive sucking at 3 months of age was evaluated by computerized apparatus. Results: EAH in high‐risk boys (mean ± standard error = 326 ± 66 kJ] was more than twice that of low‐risk boys (mean ± standard error = 151 ± 39 kJ), p = 0.03. Among girls, there was a trend for EAH to be associated with increased parental limitations on daughter snack food consumption at home (p = 0.06). EAH was unrelated to 3‐month sucking behavior. Discussion: Genes that promote childhood obesity may partially exert their influence through EAH, an effect that was limited to boys born at risk for obesity. The unique influences of genes and home environment on this trait should be disaggregated in subsequent studies.     

Using experimental ecology to understand stock enhancement: Comparisons of habitat-related predation on wild and hatchery-reared Penaeus plebejus Hess

Marine stock enhancement is often characterized by poor survival of hatchery-reared individuals due to deficiencies in their fitness, such as a diminished capacity to avoid predators. Field experiments were used to examine predation on Penaeus plebejus, a current candidate for stock enhancement in Australia. We compared overall survival of, and rates of predation on, wild P. plebejus juveniles, naïve hatchery-reared juveniles (which represented the state of individuals intended for stock enhancement) and experienced hatchery-reared juveniles (which had been exposed to natural predatory stimuli). Predation was examined in the presence of an ambush predator (Centropogon australis White, 1790) and an active-pursuit predator (Metapenaeus macleayi Haswell) within both complex (artificial macrophyte) and simple (bare sand and mud) habitats. Overall survival was lower and rates of predation were higher in simple habitats compared to complex habitats in the presence of C. australis. However, the three categories of juveniles survived at similar proportions and suffered similar rates of predation within each individual habitat. No differences in survival and rates of predation were detected among habitats or the categories of juveniles when M. macleayi was used as a predator. These results indicate that wild and hatchery-reared P. plebejus juveniles are equally capable of avoiding predators. Furthermore, exposure of hatchery-reared juveniles to wild conditions does not increase their ability to avoid predators, suggesting an innate rather than learned anti-predator response. The lower predation by C. australis in complex habitats was attributed to a reduction in this ambush predator's foraging efficiency due to the presence of structure. Ecological experiments comparing wild and hatchery-reared individuals should precede all stock enhancement programs because they may identify deficits in hatchery-reared animals that could be mitigated to optimize survival. Such studies can also identify weaknesses in wild animals, relative to hatchery-reared individuals, that may lead to the loss of resident populations.     

DBC2 is essential for transporting vesicular stomatitis virus glycoprotein

DBC2 is a tumor suppressor gene linked to breast and lung cancers. Although DBC2 belongs to the RHO GTPase family, it has a unique structure that contains a Broad-Complex/Tramtrack/Bric a Brac (BTB) domain at the C terminus instead of a typical CAAX motif. A limited number of functional studies on DBC2 have indicated its participation in diverse cellular activities, such as ubiquitination, cell-cycle control, cytoskeleton organization and protein transport. In this study, the role of DBC2 in protein transport was analyzed using vesicular stomatitis virus glycoprotein (VSVG) fused with green fluorescent protein. We discovered that DBC2 knockdown hinders the VSVG transport system in 293 cells. Previous studies have demonstrated that VSVG is transported via the microtubule motor complex. We demonstrate that DBC2 mobility depends also on an intact microtubule network. We conclude that DBC2 plays an essential role in microtubule-mediated VSVG transport from the endoplasmic reticulum to the Golgi apparatus.