Genetic analysis of sucrose concentration in soybean seeds using a historical soybean genomic panel.

KEY MESSAGE: Significant QTL for sucrose concentration have been identified using a historical soybean genomic panel, which could aid in the development of food-grade soybean cultivars. Soybean (Glycine max (L.) Merr) is a crop of global importance for both human and animal consumption, which was domesticated in China more than 6000 years ago. A concern about losing genetic diversity as a result of decades of breeding has been expressed by soybean researchers. In order to develop new cultivars, it is critical for breeders to understand the genetic variability present for traits of interest in their program germplasm. Sucrose concentration is becoming an increasingly important trait for the production of soy-food products. The objective of this study was to use a genome-wide association study (GWAS) to identify putative QTL for sucrose concentration in soybean seed. A GWAS panel consisting of 266 historic and current soybean accessions was genotyped with 76 k genotype-by-sequencing (GBS) SNP data and phenotyped in four field locations in Ontario (Canada) from 2015 to 2017. Seven putative QTL were identified on chromosomes 1, 6, 8, 9, 10, 13 and 14. A key gene related to sucrose synthase (Glyma.06g182700) was found to be associated with the QTL located on chromosome 6. This information will facilitate efforts to increase the available genetic variability for sucrose concentration in soybean breeding programs and develop new and improved high-sucrose soybean cultivars suitable for the soy-food industry.

Experience-related enhancements in striatal temporal encoding.

Temporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson's disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium spiny neurons (MSNs) via dorsal striatal microelectrode arrays in mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to "switch" response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time-related ramping activity and response-related activity increased with task experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time-related ramping activity. Finally, we found that a subset of MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.

Haplotype diversity underlying quantitative traits in Canadian soybean breeding germplasm.

KEY MESSAGE: Identification of marker-trait associations and trait-associated haplotypes in breeding germplasm identifies regions under selection and highlights changes in haplotype diversity over decades of soybean improvement in Canada. Understanding marker-trait associations using genome-wide association in soybean is typically carried out in diverse germplasm groups where identified loci are often not applicable to soybean breeding efforts. To address this challenge, this study focuses on defining marker-trait associations in breeding germplasm and studying the underlying haplotypes in these regions to assess genetic change through decades of selection. Phenotype data were generated for 175 accessions across multiple environments in Ontario, Canada. A set of 76,549 SNPs were used in the association analysis. A total of 23 genomic regions were identified as significantly associated with yield (5), days to maturity (5), seed oil (3), seed protein (5) and 100-seed weight (5), of which 14 are novel. Each significant region was haplotyped to assess haplotype diversity of the underlying genomic region, identifying ten regions with trait-associated haplotypes in the breeding germplasm. The range of genomic length for these regions (7.2 kb to 6.8 Mb) indicates variation in regional LD for the trait-associated regions. Six of these regions showed changes between eras of breeding, from historical to modern and experimental soybean accessions. Continued selection on these regions may necessitate introgression of novel parental genetic diversity as some haplotypes were fixed within the breeding germplasm. This finding highlights the importance of studying associations and haplotype diversity at a breeding program scale to understand breeders' selections and trends in soybean improvement over time. The haplotypes may also be used as a tool for selection of parental germplasm to inform breeder's decisions on further soybean improvement.

Sensory properties of yellow pea and macadamia honeys from conventional and flow hive extraction methods.

BACKGROUND: The process of harvesting honey is time consuming and labor intensive. A new system, the Flow Frame, has drastically simplified the harvesting process, enabling honey to be extracted directly from the hive with minimal processing. The sensory profile of honey is influenced, first, by botanical origin and subsequently by processing and storage parameters. A reduction in harvest processing may thus influence the sensory profile of honey harvested from FFs compared to that of honey produced from conventional processing. To test this hypothesis, two monofloral honeys (macadamia and yellow pea) were harvested from FFs, or by conventional honey extraction. Sensory profiling using conventional descriptive analysis was carried out for each floral source with an experienced trained panel. RESULTS: The two monofloral honeys harvested using the FF system had significantly (p < 0.05) higher floral and cleaner aftertaste sensory scores than the honey extracted using commercial (C) methods that involve the use of heat and centrifugation. CONCLUSION: The flow system retains honey's natural sensory properties compared to harvesting methods that require heat and centrifugation. © 2019 Society of Chemical Industry.

AP-1 and Mitf interact with NFATc1 to stimulate cathepsin K promoter activity in osteoclast precursors.

Cathepsin K (CTSK) is a secreted protease that plays an essential role in osteoclastic bone resorption and osteoporotic bone loss. We have previously shown that activator protein 1 (AP-1) stimulates CTSK promoter activity and that proximal nuclear factor of activated T cells cytoplasmic 1 (NFATc1)-binding sites play a major role in the stimulation of CTSK gene expression by receptor activator of NFκB ligand (RANKL). In the present study, we have extended these observations and further dissected the effects of transcription factors involved in the regulation of CTSK gene expression. Our aim was to investigate the cooperative interplay among transcription factors AP-1, microphthalmia-associated transcription factor (Mitf), and NFATc1, and the consequent regulatory effects on CTSK transcription. Experiments were carried out in RAW 264.7 cells, which can be readily differentiated to osteoclasts upon RANKL stimulation. Our data show that AP-1, Mitf, and NFATc1 are capable of independently stimulating CTSK promoter activity. A combination of any two factors further enhances CTSK promoter activity, with the combination of AP-1 (c-fos/c-jun) and NFATc1 inducing the largest increase. We further identify a synergistic effect when all three factors cooperate intimately at the proximal promoter region, yielding maximal transcriptional upregulation of the CTSK promoter. RANKL induces temporal localization of AP-1 and NFATc1 to the CTSK promoter. These results suggest that the interaction of multiple transcription factors mediate a maximal response to RANKL-induced CTSK gene expression.

Genome-wide genetic diversity is maintained through decades of soybean breeding in Canada.

KEY MESSAGE: Genetic diversity in Canadian soybean is maintained over decades of selection in two public breeding programs. Breeders have used a portion of the genetic diversity available in germplasm collections. Both public and private breeding efforts have been critical for the development of soybean cultivars grown around the world. Global genetic diversity of soybean has been well characterized; however, this diversity is not well studied at the breeding program scale. The objective of this study was to characterize genetic diversity over decades of breeding in two public soybean breeding programs at the University of Guelph, Canada. To address this objective, a pedigree-related panel combining 296 soybean accessions from the Ridgetown and Guelph Campus breeding programs was studied. The accessions were genotyped using genotyping-by-sequencing, imputed using the GmHapMap reference genotypes resulting in more than 3.8M SNPs, further filtered to 77k SNPs. Population structure analysis did not identify structure between the breeding programs and historical germplasm. The linkage disequilibrium decay ranged from 400 to 600 kb on average in euchromatic regions. Nucleotide diversity over decades of breeding shows that historical accessions had the highest nucleotide diversity, with significant decreases corresponding to the initial breeding activity in Canada; however, genetic diversity has increased in the last 20 years in both breeding programs. Maturity gene E2 was nearly fixed for e2 in Ridgetown accessions, while unfixed in Guelph accessions. Comparison of the breeding programs to the USDA germplasm collection reveals that breeders have only used a portion of the available genetic diversity, allowing future breeders to exploit this untapped resource. The approach used in this study may be of interest to other breeding programs for evaluating changes in genetic diversity resulting from breeding activities.

Performance Characteristics of Photoacoustic Imaging Probes with Varying Frequencies and Light-delivery Schemes.

Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that utilizes a combination of light and ultrasound to detect photoabsorbers embedded within tissues. While the clinical utility of PAI has been widely explored for several applications, limitations in light penetration and detector sensitivity have restricted these studies to mostly superficial sites. Given the importance of PA signal generation and detection on light delivery and ultrasound detector frequency, there is an ongoing effort to optimize these parameters to enhance photoabsorber detection at increased depths. With this in mind, in this study we examined performance benchmarks of a commercially available PAI/ultrasound linear array system when using different imaging frequencies and light delivery schemes. A modified light fiber jacket providing focused light delivery (FLD) at the center of the probe was compared with the built-in fiber optics lining the length of the probe. Studies were performed in vitro to compare performance characteristics such as imaging resolution, maximum imaging depth, and sensitivity to varying hematocrit concentration for each frequency and light delivery method. Monte Carlo simulations of each light delivery method revealed increased light penetration with FLD. In tissue-mimicking phantoms, vascular channels used to simulate blood vessels could be visualized at a depth of 2.4 cm when lowering imaging frequency and utilizing FLD. Imaging at lower frequencies with FLD also enabled enhanced detection of varying hematocrit concentration levels at increased depths, although lateral imaging resolution was reduced. Finally, a proof of concept in vivo probe comparison study in a mouse tumor model provided supportive evidence of our in vitro results. Collectively, our findings show that adjusting imaging frequency and applying FLD can be a straightforward approach for improving PAI performance.

Contribution of uncertainty in estimation of active drag using assisted towing method in front crawl swimming.

Active drag force in swimming can be calculated from a function of five different variables: swim velocity, tow velocity, belt force, power output and exponent of velocity. The accuracy of the drag force value is dependent on the accuracy of each variable, and on the contribution of each variable to drag estimation. To calculate uncertainty in drag value, first the derivatives of the active drag equation with respect to each variable were obtained. Second, these were multiplied by the uncertainty of that variable. Twelve national age and open level swimmers were recruited to complete four free swimming and five active drag trials. The uncertainties for the free and the tow swim velocities, and for the belt force, contributed approximately 5-6% and 2-3% error, respectively, in calculation of drag. The result of the uncertainty of the velocity exponent (1.8-2.6) indicated a contribution of about 6% error in active drag. The contribution of unequal power output showed that if a power changed 7.5% between conditions, it would lead to about 30% error in calculated drag. Consequently, if a swimmer did not maintain constant power output between conditions, there would be substantial errors in the calculation of active drag.

PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype.

BACKGROUND: Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes. METHODS: 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA. RESULTS: ER/PR- tumours demonstrated higher Kepmean and SUVmax than ER or PR+ tumours. HER2- tumours displayed higher ADCmean, Kepmean, and SUVmax than HER2+tumours. Only ADCmean discriminated Ki67⩽14% tumours (lower ADCmean) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62%; P=0.001). CONCLUSIONS: Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options.

Characterizing fluorocarbon assisted atomic layer etching of Si using cyclic Ar/C4F8 and Ar/CHF3 plasma.

With the increasing interest in establishing directional etching methods capable of atomic scale resolution for fabricating highly scaled electronic devices, the need for development and characterization of atomic layer etching processes, or generally etch processes with atomic layer precision, is growing. In this work, a flux-controlled cyclic plasma process is used for etching of SiO2 and Si at the Angstrom-level. This is based on steady-state Ar plasma, with periodic, precise injection of a fluorocarbon (FC) precursor (C4F8 and CHF3) and synchronized, plasma-based Ar+ ion bombardment [D. Metzler et al., J. Vac. Sci. Technol., A 32, 020603 (2014) and D. Metzler et al., J. Vac. Sci. Technol., A 34, 01B101 (2016)]. For low energy Ar+ ion bombardment conditions, physical sputter rates are minimized, whereas material can be etched when FC reactants are present at the surface. This cyclic approach offers a large parameter space for process optimization. Etch depth per cycle, removal rates, and self-limitation of removal, along with material dependence of these aspects, were examined as a function of FC surface coverage, ion energy, and etch step length using in situ real time ellipsometry. The deposited FC thickness per cycle is found to have a strong impact on etch depth per cycle of SiO2 and Si but is limited with regard to control over material etching selectivity. Ion energy over the 20-30 eV range strongly impacts material selectivity. The choice of precursor can have a significant impact on the surface chemistry and chemically enhanced etching. CHF3 has a lower FC deposition yield for both SiO2 and Si and also exhibits a strong substrate dependence of FC deposition yield, in contrast to C4F8. The thickness of deposited FC layers using CHF3 is found to be greater for Si than for SiO2. X-ray photoelectron spectroscopy was used to study surface chemistry. When thicker FC films of 11 Å are employed, strong changes of FC film chemistry during a cycle are seen whereas the chemical state of the substrate varies much less. On the other hand, for FC film deposition of 5 Å for each cycle, strong substrate surface chemical changes are seen during an etching cycle. The nature of this cyclic etching with periodic deposition of thin FC films differs significantly from conventional etching with steady-state FC layers since surface conditions change strongly throughout each cycle.

The Use of a Transolecranon Pin in the Treatment of Pediatric Flexion-type Supracondylar Humerus Fractures.

BACKGROUND: Flexion-type supracondylar humerus fractures are much more uncommon than their extension-type counterparts. Instability in elbow flexion renders traditional closed techniques inadequate and often results in the need for open reduction. We present a simple technique for closed reduction using a transolecranon pin for temporary stability. METHODS: A retrospective review of 9 patients treated with a transolecranon pin technique for a flexion-type supracondylar humerus fracture was performed. Operative time, need for open reduction, postoperative range of motion, final radiographic alignment using Baumann angle, and the intersection of the anterior humeral line with the capitellum was evaluated. RESULTS: All 9 patients were treated with closed reduction using a temporary transolecranon pin technique. Total surgical time averaged 38±15 minutes and was longer for type III than type II flexion-type fractures. All fractures healed by first follow-up at 1 month. There was 1 preoperative ulnar nerve deficit that resolved by the first postoperative visit. Average Baumann angle at radiographic healing was 71.2±3.3 degrees and all cases showed restoration of the normal anterior humeral line:capitellar relationship. Average postoperative flexion at final follow-up was 125 degrees and extension was 5 degrees. One patient had a flexion contracture of 10 degrees. DISCUSSION: Use of a temporary transolecranon pin allowed for closed reduction of all flexion-type fractures with no radiographic malunion. This technique is technically simple and avoids the need for open reduction or multiple fluoroscopy views. LEVEL OF EVIDENCE: Level IV-case series.

Radiographic Assessment of Guided Growth: The Correlation Between Screw Divergence and Change in Anatomic Alignment.

BACKGROUND: Assessment of changes in anatomic alignment following guided growth traditionally utilizes full-length standing radiographs which subjects patients to larger radiation doses than does a single anteroposterior radiograph of the knee. In an effort to minimize radiation exposure, the present study sought to determine whether changes in screw divergence (SD) of the 2-hole tension band plate used for hemiepiphysiodesis reliably predicts change in alignment. METHODS: A retrospective review was conducted involving all patients with genu varum or genu valgum treated with hemiepiphysiodesis at a single institution. Preoperative anatomic alignment of the femur, using anatomic lateral distal femoral angle (aLDFA) and anatomic femoral-tibial angle (aTFA), and intraoperative divergence of hemiepiphysiodesis screws were compared with postoperative imaging. Linear regression analysis determined the relationship between changes in SD and changes in alignment, and multivariate regression analysis explored the relationship between the angular changes being measured and various demographic factors. RESULTS: Linear regression analysis revealed that for every 1 degree change in SD there was a resultant 1.80 degrees of change in aTFA and 2.11 degrees of change in aLDFA. Change in aTFA is predicted by the equation: [INCREMENT]aTFA=0.41×|[INCREMENT]SD|+1.39. The change in aLDFA was predicted by the equation [INCREMENT]aLDFA=0.27×[INCREMENT]SD+1.84 with a R2 of 0.31. [INCREMENT]aTFA and [INCREMENT]SD had a correlation coefficient of 0.68 (95% confidence interval, 0.54-0.78.) [INCREMENT]aLDFA and [INCREMENT]SD had a correlation coefficient of 0.56 (95% confidence interval, 0.42-0.68). [INCREMENT]SD and sex were the only 2 independent predictors for [INCREMENT]aLDFA and [INCREMENT]aTFA as determined by multivariate regression analysis. CONCLUSION: Change in coronal plane anatomic alignment in patients being treated for genu valgum or genu varum with hemiepiphysiodesis can be reasonably estimated by measuring the change in SD. Therefore, when following patients postoperatively, focal radiographic imaging of the knee can be utilized in lieu of standing full-length limb radiographs to limit radiation to the pelvis in this sensitive patient population. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Use of a Novel Pathway for Early Discharge Was Associated With a 48% Shorter Length of Stay After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

INTRODUCTION: Hospital stay after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has decreased only modestly over time despite a healthy patient population. The purpose of this study was to evaluate the impact of a novel postoperative pathway on length of stay (LOS) and complications. METHODS: A retrospective review of patients undergoing PSF for AIS in 2011 to 2012 was performed at 2 institutions evaluating demographics, preoperative Cobb angles, surgical duration, blood loss, LOS, and postoperative complications. Patients at one center were managed using an accelerated discharge (AD) pathway emphasizing early transition to oral pain medications mobilization with physical therapy 2 to 3 times/d, and discharge regardless of return of bowel function. Expectations were set with the family before surgery for early discharge. Patients at the other center were managed without a standardized pathway. RESULTS: One hundred five patients underwent PSF and were treated by an AD pathway, whereas 45 patients were managed using a traditional discharge (TD) pathway. There was no difference in proximal thoracic and main thoracic Cobb magnitudes and a small difference in thoracolumbar curve magnitudes (35.2±13.0 degrees AD vs. 40.6±11.4 degrees TD, P=0.004) between groups. Surgical time was slightly shorter in AD patients (median 3.1 vs. 3.9 h, P=0.0003) with no difference in estimated blood loss. LOS was 48% shorter in the AD group (2.2 vs. 4.2 d, P<0.0001). There was no difference in readmissions or wound complications between groups. CONCLUSIONS: Hospital stay was nearly 50% shorter in patients managed by the AD pathway without any increase in readmissions or early complications. SIGNIFICANCE: Discharge after PSF for AIS may be expedited using a coordinated postoperative pathway. No increase in complications was seen using the AD pathway. Earlier discharge may reduce health care costs and allow an earlier return to normalcy for families. LEVEL OF EVIDENCE: Level III-case control study.

The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States.

BACKGROUND: The effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs). METHODS: To evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040. RESULTS: Increasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%. CONCLUSIONS: Interferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States.

Valence Band Dependent Charge Transport in Bulk Molecular Electronic Devices Incorporating Highly Conjugated Multi-[(Porphinato)Metal] Oligomers.

Molecular electronics offers the potential to control device functions through the fundamental electronic properties of individual molecules, but realization of such possibilities is typically frustrated when such specialized molecules are integrated into a larger area device. Here we utilize highly conjugated (porphinato)metal-based oligomers (PM(n) structures) as molecular wire components of nanotransfer printed (nTP) molecular junctions; electrical characterization of these "bulk" nTP devices highlights device resistances that depend on PM(n) wire length. Device resistance measurements, determined as a function of PM(n) molecular length, were utilized to evaluate the magnitude of a phenomenological ß corresponding to the resistance decay parameter across the barrier; these data show that the magnitude of this ß value is modulated via porphyrin macrocycle central metal atom substitution [ß(PZn(n); 0.065 Å(-1)) < ß(PCu(n); 0.132 Å(-1)) < ß(PNi(n); 0.176 Å(-1))]. Cyclic voltammetric data, and ultraviolet photoelectron spectroscopic studies carried out at gold surfaces, demonstrate that these nTP device resistances track with the valence band energy levels of the PM(n) wire, which were modulated via porphyrin macrocycle central metal atom substitution. This study demonstrates the ability to fabricate "bulk" and scalable electronic devices in which function derives from the electronic properties of discrete single molecules, and underscores how a critical device function--wire resistance--may be straightforwardly engineered by PM(n) molecular composition.

HIV testing at a community health center before and after implementing universal screening.

This study analyzed the quality of HIV screening at one of the largest community health centers in Connecticut. The data indicated that implementing universal HIV screening increased the proportion of underrepresented minorities and women tested, reducing the HIV testing disparities that previously existed at this center.

Blood-based lung cancer biomarkers identified through proteomic discovery in cancer tissues, cell lines and conditioned medium.

BACKGROUND: Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging. RESULTS: We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21-1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775). CONCLUSIONS: Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.

Acquired cutis laxa associated with cutaneous mastocytosis.

Cutis laxa is characterized by dramatic wrinkling of skin that is lacking in elasticity due to inherent defects in dermal elastic fibers. Cutis laxa can be caused by genetic and metabolic disorders. It can also be acquired, possibly resulting from inflammatory processes with destruction of elastic fibers. This report describes a 26-year old woman who developed acquired cutis laxa and cutaneous mastocytosis leading to premature aging. She represents a unique co-occurrence of these two separate disease entities. To our knowledge, there has been only one published case report of acquired cutis laxa occurring in association with urticaria pigmentosa in a 4-year old girl. Our case would be a second case that exhibits the coexistence of these two disorders in an adult female.

Genome sequencing and analysis of the paclitaxel-producing endophytic fungus Penicillium aurantiogriseum NRRL 62431.

BACKGROUND: Paclitaxel (Taxol™) is an important anticancer drug with a unique mode of action. The biosynthesis of paclitaxel had been considered restricted to the Taxus species until it was discovered in Taxomyces andreanae, an endophytic fungus of T. brevifolia. Subsequently, paclitaxel was found in hazel (Corylus avellana L.) and in several other endophytic fungi. The distribution of paclitaxel in plants and endophytic fungi and the reported sequence homology of key genes in paclitaxel biosynthesis between plant and fungi species raises the question about whether the origin of this pathway in these two physically associated groups could have been facilitated by horizontal gene transfer. RESULTS: The ability of the endophytic fungus of hazel Penicillium aurantiogriseum NRRL 62431 to independently synthesize paclitaxel was established by liquid chromatography-mass spectrometry and proton nuclear magnetic resonance. The genome of Penicillium aurantiogriseum NRRL 62431 was sequenced and gene candidates that may be involved in paclitaxel biosynthesis were identified by comparison with the 13 known paclitaxel biosynthetic genes in Taxus. We found that paclitaxel biosynthetic gene candidates in P. aurantiogriseum NRRL 62431 have evolved independently and that horizontal gene transfer between this endophytic fungus and its plant host is unlikely. CONCLUSIONS: Our findings shed new light on how paclitaxel-producing endophytic fungi synthesize paclitaxel, and will facilitate metabolic engineering for the industrial production of paclitaxel from fungi.

Lung transplantation in adults and children: putting lung function into perspective.

The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. Spirometry and the evaluation of forced expiratory volume in 1 s and forced vital capacity, remain core indices that are measured as part of routine clinical follow-up. Spirometry, while reproducible in detecting lung allograft dysfunction, lacks specificity in differentiating the different complications of lung transplantation such as rejection, infection and bronchiolitis obliterans. However, interpretation of spirometry is central to defining the different 'chronic rejection' phenotypes. It is becoming apparent that the maximal lung function achieved following transplantation, as measured by spirometry, is influenced by a number of donor and recipient factors as well as the type of surgery performed (single vs double vs lobar lung transplant). In this review, we discuss the wide range of variables that need to be considered when interpreting lung function testing in lung transplant recipients. Finally, we review a number of novel measurements of pulmonary function that may in the future serve as better biomarkers to detect and diagnose the cause of the failing lung allograft.