Phox2b-expressing neurons contribute to breathing problems in Kcnq2 loss- and gain-of-function encephalopathy models.

Loss- and gain-of-function variants in the gene encoding KCNQ2 channels are a common cause of developmental and epileptic encephalopathy, a condition characterized by seizures, developmental delays, breathing problems, and early mortality. To understand how KCNQ2 dysfunction impacts behavior in a mouse model, we focus on the control of breathing by neurons expressing the transcription factor Phox2b which includes respiratory neurons in the ventral parafacial region. We find Phox2b-expressing ventral parafacial neurons express Kcnq2 in the absence of other Kcnq isoforms, thus clarifying why disruption of Kcnq2 but not other channel isoforms results in breathing problems. We also find that Kcnq2 deletion or expression of a recurrent gain-of-function variant R201C in Phox2b-expressing neurons increases baseline breathing or decreases the central chemoreflex, respectively, in mice during the light/inactive state. These results uncover mechanisms underlying breathing abnormalities in KCNQ2 encephalopathy and highlight an unappreciated vulnerability of Phox2b-expressing ventral parafacial neurons to KCNQ2 pathogenic variants.

Neonatal encephalopathy: Focus on epidemiology and underexplored aspects of etiology.

Neonatal Encephalopathy (NE) is a neurologic syndrome in term and near-term infants who have depressed consciousness, difficulty initiating and maintaining respiration, and often abnormal tone, reflexes and neonatal seizures in varying combinations. Moderate/severe NE affects 0.5-3/1000 live births in high-income countries, more in low- and middle-income countries, and carries high risk of mortality or disability, including cerebral palsy. Reduced blood flow and/or oxygenation around the time of birth, as with ruptured uterus, placental abruption or umbilical cord prolapse can cause NE. This subset of NE, with accompanying low Apgar scores and acidemia, is termed Hypoxic-Ischemic Encephalopathy. Other causes of NE that can present similarly, include infections, inflammation, toxins, metabolic disease, stroke, placental disease, and genetic disorders. Aberrant fetal growth and congenital anomalies are strongly associated with NE, suggesting a major role for maldevelopment. As new tools for differential diagnosis emerge, their application for prevention, individualized treatment and prognostication will require further systematic studies of etiology of NE.

Impaired white matter development in extremely low-birth-weight infants with previous brain hemorrhage.

BACKGROUND AND PURPOSE: Brain hemorrhage is common in premature infants. The purpose of the study is to evaluate white matter development in extremely low-birth-weight infants with or without previous brain hemorrhage. MATERIALS AND METHODS: Thirty-three extremely low-birth-weight infants were prospectively enrolled and included in this institutional review board-approved study. Another 10 healthy term infants were included as controls. The medical records of the extremely low-birth-weight infants were reviewed for sonography diagnosis of intraventricular hemorrhage. All infants had an MR imaging examination at term-equivalent age for detection of previous hemorrhage, and their white matter was scored and compared among different groups. DTI measured fractional anisotropy values were also compared voxelwise by tract-based spatial statistics. RESULTS: Compared with controls, the white matter score was not significantly different in extremely low-birth-weight infants without blood deposition on MR imaging (P = .17), but was significantly worse in extremely low-birth-weight infants with blood deposition on MR imaging but no intraventricular hemorrhage diagnosis by sonography (P = .02), in extremely low-birth-weight infants with grade 1 or 2 intraventricular hemorrhage on sonography (P = .003), and in extremely low-birth-weight infants with grade 3 or 4 intraventricular hemorrhage on sonography (P = .0001). Extremely low-birth-weight infants without blood deposition on MR imaging did not show any white matter regions with significantly lower fractional anisotropy values than controls. Extremely low-birth-weight infants with blood deposition on MR imaging, but no intraventricular hemorrhage diagnosis, did show white matter regions with significantly lower fractional anisotropy values, and extremely low-birth-weight infants with intraventricular hemorrhage diagnosis had widespread white matter regions with lower fractional anisotropy values. CONCLUSIONS: Previous brain hemorrhage is associated with abnormal white matter in extremely low-birth-weight infants at term-equivalent age, and sonography is not sensitive to minor hemorrhages that are sufficient to cause white matter injury.

QTL mapping for yield and lodging resistance in an enhanced SSR-based map for tef.

Tef is a cereal crop of cultural and economic importance in Ethiopia. It is grown primarily for its grain though it is also an important source of fodder. Tef suffers from lodging that reduces both grain yield and quality. As a first step toward executing a marker-assisted breeding program for lodging resistance and grain yield improvement, a linkage map was constructed using 151 F(9) recombinant inbred lines obtained by single-seed-descent from a cross between Eragrostis tef and its wild relative Eragrostis pilosa. The map was primarily based on microsatellite (SSR) markers that were developed from SSR-enriched genomic libraries. The map consisted of 30 linkage groups and spanned a total length of 1,277.4 cM (78.7% of the genome) with an average distance of 5.7 cM between markers. This is the most saturated map for tef to date, and for the first time, all of the markers are PCR-based. Using agronomic data from 11 environments and marker data, it was possible to map quantitative trait loci (QTL) controlling lodging, grain yield and 15 other related traits. The positive effects of the QTL identified from the wild parent were mainly for earliness, reduced culm length and lodging resistance. In this population, it is now possible to combine lodging resistance and grain yield using a marker-assisted selection program targeting the QTL identified for both traits. The newly developed SSR markers will play a key role in germplasm organization, fingerprinting and monitoring the success of the hybridization process in intra-specific crosses lacking distinctive morphological markers.

Influences of heterotrophic and autotrophic resource use on carbon and hydrogen isotopic compositions of tropical tree leaves.

The delta13C and SD values of newly emerging to senescing tree leaves produced during a rainy season were obtained in dry seasonal and moist forest in Panamá. Newly emerging leaves had less negative delta13C values than older leaves yet instantaneous pi/pa was never lowest in the youngest leaves. Furthermore, isotopic enrichment during early growth may have a detectable influence on the delta13C values of mature leaves. The deltaD values of cellulose nitrate were only related to deltaD values of leaf water if leaf age was also considered so that, for a given deltaD of leaf water, deltaD values were highest in the youngest leaves (R2 = 98%). There was no correlation between leaf age and deltaD values of leaf water. Investment of translocated organic carbon is a factor likely to be associated with both 13C and deuterium enrichment effects in new leaves. A coarse, mass balance approach can estimate the proportional heterotrophic investment in leaf growth and improve estimates of integrated pi/pa by approximating delta13C for the most autotrophic phase of leaf growth. Delta13C values of the predominantly sucrose mobile organic fraction in new leaves were less negative than in older leaves, thereby suggesting that the enrichment did not occur at the original site of production of the substrate for new leaf growth. Although the delta values of early leaf growth must be influenced by inputs of translocated organic carbon, enrichment effects, per se, are apparently caused by other mechanisms such as, for carbon, de novo sucrose synthesis and anaplerotic replenishment. Better recognition of metabolic causes of isotopic enrichment in leaves promises to increase the power and accuracy of inferences about carbon and water use of tropical trees from delta analyses.

The effect of endovascular irradiation on platelet recruitment at sites of balloon angioplasty in pig coronary arteries.

BACKGROUND: Endovascular irradiation (EI) inhibits balloon-induced neointima formation in animals and is now in clinical trials for restenosis prevention. However, little is known of the effect of EI on vessel thrombogenicity due to delayed arterial healing. We investigated EI effects on platelet recruitment in pig coronary arteries. METHODS AND RESULTS: EI was performed using (90)Sr/Y at 0 Gray (Gy), 15Gy, or 30Gy at 2 mm after balloon overstretch injury. At 1 day, 1 week, and 1 month, platelet recruitment and thrombus formation were assessed using autologous (111)In-oxine-platelet labeling and light and scanning electron microscopy. In balloon-injured nonirradiated vessels, there was complete reendothelialization at 1 month, and platelet recruitment was similar to normal uninjured arteries. In irradiated vessels, scanning electron microscopy showed incomplete reendothelialization at 1 month, and these areas demonstrated attachment of activated platelets. Light microscopy of irradiated coronaries showed adherent partially organized thrombi and incomplete resolution of intramural hemorrhages. There was a significant increase in platelet recruitment at 1 month in arteries receiving EI at 15Gy (5.1+/-2. 8x10(6), P=0.02) or 30Gy (12.5+/-9.9x10(6), P=0.005) compared with nonirradiated controls (2.7+/-1.5x10(6)); 30Gy was also higher than 15Gy (P=0.05). Platelet recruitment was also increased for 30Gy compared with control at 1 day. CONCLUSIONS: Endovascular irradiation at 15Gy or 30Gy after balloon angioplasty results in incomplete endothelial recovery, impaired resolution of intramural hemorrhage, and a dose-dependent increase in platelet recruitment at 1 month.

Decline of photosynthetic capacity with leaf age in relation to leaf longevities for five tropical canopy tree species.

The effect of leaf aging on photosynthetic capacities was examined for upper canopy leaves of five tropical tree species in a seasonally dry forest in Panama. These species varied in mean leaf longevity between 174 and 315 d, and in maximum leaf life span between 304 and 679 d. The light-saturated CO2 exchange rates of leaves produced during the primary annual leaf flush measured at 7-8 mo of age were 33-65% of the rates measured at 1-2 mo of age for species with leaf life span of < 1 yr. The negative regression slopes of photosynthetic capacity against leaf age were steeper for species with shorter maximum leaf longevity. In all species, regression slopes were less steep than the slopes predicted by assuming a linear decline toward the maximum leaf age (20-80% of the predicted decline rate). Maximum oxygen evolution rates and leaf nitrogen content declined faster with age for species with shorter leaf life spans. Statistical significance of regression slopes of oxygen evolution rates against leaf age was strongest on a leaf mass basis (r = 0.49-0.87), followed by leaf nitrogen basis (r = 0.48-0.77), and weakest on a leaf area basis (r = 0.35-0.70).

Plant physiological ecology of tropical forest canopies.

Mechanistic information about tropical canopy function is emerging at the leaf, tree, stand and landscape levels. With improved canopy access, comprehensive data are accumulating about seasonal and spatial variation in light, temperature and humidity, and corresponding variation in leaf carbon gain and water loss. At the whole-plant level, simultaneous measurements at different spatial scales have revealed the role of boundary layer dynamics in regulating transpiration. Emergent properties of canopy function are being explored through models that integrate leaf and landscape-level exchange processes. Integration of exchange processes that include functional diversity at different scales has the potential to validate regional estimates of gas exchange, which are critical to our understanding of the role of tropical forests in global atmospheric carbon balance.

Contrasting leaf phenotypes control seasonal variation in water loss in a tropical forest shrub.

Psychotria marginata, a shrub common to humid tropical forests in Central America, produces leaves in two seasonal flushes with contrasting morphology and physiology. Leaf production is bimodal with a major peak at the beginning of the annual wet season and a secondary peak at the end of the wet season. Together these peaks account for 75-87% of annual leaf production. Leaves produced just prior to the dry season have higher specific mass and, during drought, have lower stomatal conductances and higher water-use efficiencies. Plants irrigated during two consecutive dry seasons continued to produce leaves with these morphological and physiological differences, indicating that this feature has been strongly canalized by some factor other than water availability in this highly predictable yet seasonal habitat. The bimodal leaf production results in acclimation to changing conditions through co-occurring leaves that lack the physiological plasticity usually associated with acclimation. Heterophylly of this form suggests that the moderate drought of the dry season has been a significant selective factor for understory plants.