High Thoracic Tortuosity Is Associated With CT-Markers of Degeneration of the Descending Thoracic Aortic Wall.

OBJECTIVE/INTRODUCTION: Increased vascular tortuosity may be an independent marker of generalized aortic pathology. This study investigates the association between descending thoracic aortic tortuosity, aneurysm pathophysiology, and outcomes following EVAR in AAA patients. METHODS: Patients who underwent elective EVAR between 2004 and 2018 were reviewed. Thoracic tortuosity index (TTI) was measured using 3D reconstruction software. Patients were dichotomized across the median TTI into high tortuosity [HT] (TTI >1.27, Figure1(a)) and low tortuosity [LT] (TTI ≤1.27, Figure 1(b)) groups. Perioperative complications, postoperative outcomes, and CT-based features of thoracic aortic wall degeneration (Figure 1(c)-(e)) were collected and analyzed. RESULTS: 136 patients underwent treatment: 70 HT patients, including 54 males and 16 females (mean age: 77 years), and 66 LT patients, including 62 males and 4 females (mean age: 70 years) (age; P < .001). LT patients exhibited greater prevalence of hypercholesterolemia and diabetes (P = .045, P = .01). Presence of degenerative aortic wall markers was greater in HT patients (P = .045). HT patients had higher incidence of multiple aneurysms concurrently present in their aorta compared to LT (32.8% vs 11.3%; P = .002). Frequency of AAA rupture/dissection was 4.3% for HT and 1.5% for LT (P = .339). A trend was observed in all cause 30-day mortality in the HT group (P = .061). Other perioperative complications and postoperative outcomes were similar between groups. CONCLUSION: High TTI was associated with older age at time of EVAR, greater prevalence of degenerative markers in the descending thoracic aortic wall, and widespread aorto-iliac dilation. While not predictive of EVAR outcomes, TTI can provide valuable information regarding aneurysm pathophysiology.

Sustainable irrigation based on co-regulation of soil water supply and atmospheric evaporative demand.

Irrigation is an important adaptation to reduce crop yield loss due to water stress from both soil water deficit (low soil moisture) and atmospheric aridity (high vapor pressure deficit, VPD). Traditionally, irrigation has primarily focused on soil water deficit. Observational evidence demonstrates that stomatal conductance is co-regulated by soil moisture and VPD from water supply and demand aspects. Here we use a validated hydraulically-driven ecosystem model to reproduce the co-regulation pattern. Specifically, we propose a plant-centric irrigation scheme considering water supply-demand dynamics (SDD), and compare it with soil-moisture-based irrigation scheme (management allowable depletion, MAD) for continuous maize cropping systems in Nebraska, United States. We find that, under current climate conditions, the plant-centric SDD irrigation scheme combining soil moisture and VPD, could significantly reduce irrigation water use (-24.0%) while maintaining crop yields, and increase economic profits (+11.2%) and irrigation water productivity (+25.2%) compared with MAD, thus SDD could significantly improve water sustainability.

Whole genome sequencing identifies loci specifically associated with thoracic aortic wall defects and abdominal aortic aneurysms in patients with European ancestry.

OBJECTIVE: The objective of this study was to better understand the pathophysiology and underlying genetic mechanisms behind two abdominal aortic aneurysm (AAA) subtypes using computed tomographic imaging in combination with whole genome sequencing. METHODS: Patients with a known AAA and European ancestry were included in this investigation and underwent genetic and image analysis. Patients with AAAs and indications of descending thoracic aortic pathology (aortic dissection, penetrating aortic ulcers, intramural hematoma, atheromas, ulcerative plaque, and intramural ulceration, and intimal flaps/tears) were classified as having thoracic aortic disease, grouped together, and compared with patients with an AAA and a normal descending thoracic aorta. Whole genome sequencing was then performed on the 93 patients who had imaging features consistent with thoracic aortic disease and the 126 patients with a normal descending thoracic aorta. RESULTS: The results of this study suggest one variant-level, four gene-level, and one gene set-level associations in patients with thoracic aortic disease who also had an AAA. The variant rs79508780 located in TSEN54 achieved study-wide significance (P = 1.71E-06). BATF3 and SMLR1 were significantly associated and EFCAB3 and TAF4 were reached suggestive assocation with a diseased descending thoracic aorta (P = 5.23E-26, P = 1.86E-25, P = 1.54E-05, and P = 8.31E-05, respectively). Gene sets were also compiled using MSigDB and trait-based index single nucleotide variation from major genome-wide association studies. GO_DNA_DOUBLE_STRAND_BREAK_PROCESSING, a gene set related to double-stranded DNA break repair, was significantly associated with thoracic aortic disease in AAA patients (P = 1.80E-06). CONCLUSIONS: This pilot study provides further evidence that an AAA may be the end result of multiple degenerative pathways. Genetic variations in vitamin D signaling, cholesterol metabolism, extracellular matrix breakdown, and double-stranded DNA break repair pathways were associated with European patients who had an AAA and thoracic aortic disease. Additionally, this study provides support for the application of a radiogenomic approach for the investigation of other potential pathologies that could lead to the development of an AAA or influence future management decisions. (JVS-Vascular Science.). CLINICAL RELEVANCE: In this study, we provide evidence that abdominal aortic aneurysms (AAAs) may be a result of multiple pathophysiologies rather than a single disease. We have identified genetic variants involved in vitamin D signaling, cholesterol metabolism, extracellular matrix breakdown, and double-stranded DNA break repair associated with structural defects in the aortic wall in patients with AAAs who are of European descent. Patients with AAAs and structural defects in the thoracic aorta have been previously linked to differential behavior after endovascular aneurysm repair. These patients with wall defects exhibited greater sac regression, a marker of surgical success, after endovascular aneurysm repair. Our study demonstrates the usefulness of a radiogenomic approach for elucidating mechanisms behind the formation and future behavior of AAAs that could aid surgeons in making future procedural and management decisions.

Decreased Abdominal Aortic Aneurysm Size Following EVAR in Patients With CT Evidence of Subclinical Thoracic Aortic Dissection.

BACKGROUND: Aneurysm sac regression following endovascular repair (EVAR) of an abdominal aortic aneurysm (AAA) is an established indicator of surgical success. However, even with a completely excluded aneurysm, the degree of aortic sac regression may vary. This study evaluates the relationship between aneurysm sac regression after EVAR and the presence of morphological features in the thoracic aorta that can be associated with a subclinical aortic dissection, termed dissection morphology in this study. METHODS: Patients who underwent EVAR to repair an infrarenal aortic aneurysm at Mount Sinai Hospital between 1996 and 2017 with a postoperative CT scan and a 3-year follow-up scan available for analysis were included in the study. Patients with a type I or type III endoleak were not included. The thoracic aorta was evaluated for dissection morphology on CT scan, which included the presence of aortic dissection, penetrating aortic ulcers, and intramural hematomas. AAA sac regression after EVAR was compared between patients with dissection morphology (n = 157) and patients without those characteristics (n = 141). An independent investigator performed the CT analysis and was blinded to the degree of sac regression. RESULTS: Demographics and comorbid clinical conditions were compared between patients with and without dissection morphology. There were no significant differences in age, gender, smoking habits, or cardiovascular conditions. The median AAA diameter after EVAR, over the course of the study, in patients with dissection morphology decreased by 11.30 mm (-17.20, -3.60) compared to a median change of 0.30 mm (-8.60, 8.60) in patients without dissection morphology features (p < 0.001). Patients with dissection morphology also had fewer type II endoleaks in postoperative follow-up scans (22.9% vs. 53.9%, p < 0.001). Additionally, patients with dissection morphology had longer EVAR operative times (192.00 min [167.25, 230.00] vs.174.00 min [150.00, 215.00], p = 0.004). AAA-related mortality after 3 years was not significantly different between the 2 groups (p = 1.0). CONCLUSIONS: The presence of imaging features consistent with dissection morphology in the thoracic aorta correlated with greater AAA sac regression and fewer type II endoleaks after EVAR. Assessing these imaging features in patients undergoing EVAR may be useful in understanding aneurysm behavior in terms of aneurysm growth, risk of rupture, and outcomes following endovascular surgery. Identifying differential rates of aneurysm sac regression may have implications regarding the role of subclinical dissections in the etiology of AAA development.

Seasonal responses of photosynthetic parameters in maize and sunflower and their relationship with leaf functional traits.

Estimates of seasonal variation in photosynthetic capacity (Pc ) are critical for modeling the time course of carbon fluxes. Given the time-intensive nature of calculating Pc parameters via gas exchange, it is appealing to calculate parameter variation via changes in chlorophyll (Chl) and nitrogen (N) content by assuming that Pc scales with these variables. Although seasonal changes in Pc and the relationships between N and Pc have been evaluated in forest canopies, there is limited data on seasonal parameter values in crops, nor is it clear if seasonal changes in Pc can be estimated from leaf traits under the high N fertility of managed systems. We characterized the seasonal variability of the maximum rates of carboxylation (Vcmax ) and electron transport (Jmax ) under well-fertilized conditions for maize (Zea mays L.) and sunflower (Helianthus annuus L.) and coupled these data with measurements of Chl, N, and leaf mass per unit area (LMA). The seasonal Chl-N relationship was significant in maize, but not in sunflower. Area-based N-Vcmax relationships were not significant for either crop. Mass-based N-Vcmax relationships were weak in sunflower, but highly significant in maize. Our results suggest that Pc can be seasonally adjusted in maize with reliable estimates of changes in LMA.

Seasonal variability of the parameters of the Ball-Berry model of stomatal conductance in maize (Zea mays L.) and sunflower (Helianthus annuus L.) under well-watered and water-stressed conditions.

The Ball-Berry (BB) model of stomatal conductance (gs ) is frequently coupled with a model of assimilation to estimate water and carbon exchanges in plant canopies. The empirical slope (m) and 'residual' gs (g0 ) parameters of the BB model influence transpiration estimates, but the time-intensive nature of measurement limits species-specific data on seasonal and stress responses. We measured m and g0 seasonally and under different water availability for maize and sunflower. The statistical method used to estimate parameters impacted values nominally when inter-plant variability was low, but had substantial impact with larger inter-plant variability. Values for maize (m = 4.53 ± 0.65; g0  = 0.017 ± 0.016 mol m-2 s-1 ) were 40% higher than other published values. In maize, we found no seasonal changes in m or g0 , supporting the use of constant seasonal values, but water stress reduced both parameters. In sunflower, inter-plant variability of m and g0 was large (m = 8.84 ± 3.77; g0  = 0.354 ± 0.226 mol m-2 s-1 ), presenting a challenge to clear interpretation of seasonal and water stress responses - m values were stable seasonally, even as g0 values trended downward, and m values trended downward with water stress while g0 values declined substantially.

Estimating the sensitivity of stomatal conductance to photosynthesis: a review.

A common approach for estimating fluxes of CO2 and water in canopy models is to couple a model of photosynthesis (An ) to a semi-empirical model of stomatal conductance (gs ) such as the widely validated and utilized Ball-Berry (BB) model. This coupling provides an effective way of predicting transpiration at multiple scales. However, the designated value of the slope parameter (m) in the BB model impacts transpiration estimates. There is a lack of consensus regarding how m varies among species or plant functional types (PFTs) or in response to growth conditions. Literature values are highly variable, with inter-species and intra-species variations of >100%, and comparisons are made more difficult because of differences in collection techniques. This paper reviews the various methods used to estimate m and highlights how variations in measurement techniques or the data utilized can influence the resultant m. Additionally, this review summarizes the reported responses of m to [CO2 ] and water stress, collates literature values by PFT and compiles nearly three decades of values into a useful compendium.

An update on the etiology of abdominal aortic aneurysms: implications for future diagnostic testing.

Abdominal aortic aneurysm (AAA) disease is multifactorial with both environmental and genetic risk factors. The current research in AAA revolves around genetic profiles and expression studies in both human and animal models. Variants in genes involved in extracellular matrix degradation, inflammation, the renin-angiotensin system, cell growth and proliferation and lipid metabolism have been associated with AAA using a variety of study designs. However, the results have been inconsistent and without a standard animal model for validation. Thus, despite the growing body of knowledge, the specific variants responsible for AAA development, progression and rupture have yet to be determined. This review explores some of the more significant genetic studies to provide an overview of past studies that have influenced the current understanding of AAA etiology. Expanding our understanding of disease pathogenesis will inform research into novel diagnostics and therapeutics and ultimately to improve outcomes for patients with AAA.

An Evolving Understanding of the Genetic Causes of Abdominal Aortic Aneurysm Disease.

Aneurysms of the abdominal aorta (AAA) are relatively common - affecting as many as 8% of men and 1% of women over the age of 65. AAAs are characterized by a 50% increase in the diameter of the aneurysmal aorta compared with the normal vessel. Degeneration of structural components of the aortic wall is believed to be central in the pathogenesis of AAAs. The exact mechanism of degeneration is not well characterized, although degradation of elastin and collagen has been clearly shown. At least six genetic variants have been associated with AAA in genome-wide association studies: CDKN2BAS1, DAB2IP, LDLR, LRP1, SORT1, and IL6R. These variants reach genome-wide significance; however, they have not been replicated in multiple cohorts, nor have they been clearly shown to be disease causative. AAA is a challenging disease for investigation because it is most often asymptomatic and generally has a late disease onset, making it difficult to diagnose. Determination of the genetic mechanism behind aneurysm formation, progression, and rupture crosses disciplines requiring input from multiple fields of study, larger patient cohorts, and the evolving modalities of genetic testing.

Solution structure of the HIV-1 exon splicing silencer 3.

Alternative splicing of the human immunodeficiency virus type 1 (HIV-1) genomic RNA is necessary to produce the complete viral protein complement, and aberrations in the splicing pattern impair HIV-1 replication. Genome splicing in HIV-1 is tightly regulated by the dynamic assembly/disassembly of trans host factors with cis RNA control elements. The host protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A1, regulates splicing at several highly conserved HIV-1 3' splice sites by binding 5'-UAG-3' elements embedded within regions containing RNA structure. The physical determinants of hnRNP A1 splice site recognition remain poorly defined in HIV-1, thus precluding a detailed understanding of the molecular basis of the splicing pattern. Here, the three-dimensional structure of the exon splicing silencer 3 (ESS3) from HIV-1 has been determined using NMR spectroscopy. ESS3 adopts a 27-nucleotide hairpin with a 10-bp A-form stem that contains a pH-sensitive A(+)C wobble pair. The seven-nucleotide hairpin loop contains the high-affinity hnRNP-A1-responsive 5'-UAGU-3' element and a proximal 5'-GAU-3' motif. The NMR structure shows that the heptaloop adopts a well-organized conformation stabilized primarily by base stacking interactions reminiscent of a U-turn. The apex of the loop is quasi-symmetric with UA dinucleotide steps from the 5'-GAU-3' and 5'-UAGU-3' motifs stacking on opposite sides of the hairpin. As a step towards understanding the binding mechanism, we performed calorimetric and NMR titrations of several hnRNP A1 subdomains into ESS3. The data show that the UP1 domain forms a high-affinity (K(d)=37.8±1.1 nM) complex with ESS3 via site-specific interactions with the loop.