Validation of a new automatic smoking machine to study the effects of cigarette smoke in newborn lambs

The aim of this study was to describe the characteristics and validate the use of a new, custom-built automatic smoking machine (ASM), primarily designed to study the effects of an environmental tobacco smoke surrogate (ETS surrogate) exposure in animals of various sizes, including large animals. The equipment includes a programmable ASM coupled to a vented whole body chamber, where animals can be exposed to both mainstream and sidestream smoke. The user-friendly interface allows for full programming of puff volume (1-60 mL), time interval between two puffs (1-60 s) and between two cigarettes (1-60 min). Eight newborn lambs were exposed to either 10 (4 lambs, C10 group) or 20 (4 lambs, C20 group) cigarettes, 8 h per day for 15 days. Four additional control, lambs were exposed to air (C0 group). Weight gain was identical in all three groups of lambs. Urinary cotinine/creatinine ratio increased with the number of cigarettes smoked (C0: 11 ± 7 ng/mg; C10: 961 ± 539 ng/mg; C20: 1821 ± 312 ng/mg), with levels in the C10 and C20 groups in keeping with values published in infants exposed to ETS. Overall, results show that our new ASM is especially well suited for ETS surrogate exposure in non-restrained, non-anaesthetized large animals such as sheep

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Computer simulation of breast reduction surgery

Background: Plastic surgery of the breast, particularly breast reduction, is considered difficult. It can become a challenge for a less experienced surgeon to understand exactly what to do when facing a particular type of breast and how to avoid unsatisfactory results. Methods: The goal of this study was to create a computer model of the breast that provides a basis for the simulation of breast surgery, particularly breast reduction. The reconstruction of elastic parameters is based on observations of the breast with the patient in different positions. Results: It is shown that several measurements with the patient in different positions allow one to choose the parameters of the model and determine the elastic coefficients of the breast and the skin. The geometry of the breast before and after surgery is simulated. A qualitative study of the incision parameters’ influence on the final geometry of the breast is presented. Conclusion: The developed methodology and software allow one to estimate the form of the breast after the surgery by knowing its form before surgery and taking into consideration the parameters of incision applied by the surgeon at the time of surgery. The described approach can be used for the qualitative and quantitative study of breast reduction surgery with a satisfactory result. Level of Evidence: V (This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Clinical and Virological Features of Dengue in Vietnamese Infants

Dengue is a major public health problem in tropical and subtropical countries, including Vietnam. Dengue cases occur in children and young adults; however, severe dengue also occurs in infants less than 1 year of age. Prompt recognition of dengue is important for appropriate case management, particularly in infants in whom febrile illness from other causes is common. We describe the clinical picture, virological and immunological characteristics of infants with dengue admitted to three hospitals in southern Vietnam, compared with infants admitted with fever not due to dengue. We show that infants with dengue are difficult to distinguish from those with other febrile illnesses based on signs and symptoms at presentation, and so laboratory tests to confirm dengue virus infection may be useful for diagnosis and management. Conventional diagnostic methods for dengue have low sensitivity early in infection, and we show that an alternative antigen-detection assay that has demonstrated good sensitivity and specificity in older age groups also performs well in infants. This study will help to inform the diagnosis and management of dengue in infants

Reduced Exercise Tolerance and Pulmonary Capillary Recruitment with Remote Secondhand Smoke Exposure

RATIONALE: Flight attendants who worked on commercial aircraft before the smoking ban in flights (pre-ban FAs) were exposed to high levels of secondhand smoke (SHS). We previously showed never-smoking pre-ban FAs to have reduced diffusing capacity (Dco) at rest. METHODS: To determine whether pre-ban FAs increase their Dco and pulmonary blood flow (Qc) during exercise, we administered a symptom-limited supine-posture progressively increasing cycle exercise test to determine the maximum work (watts) and oxygen uptake (VO2) achieved by FAs. After 30 min rest, we then measured Dco and Qc at 20, 40, 60, and 80 percent of maximum observed work. RESULTS: The FAs with abnormal resting Dco achieved a lower level of maximum predicted work and VO2 compared to those with normal resting Dco (mean±SEM; 88.7±2.9 vs. 102.5±3.1%predicted VO2; p = 0.001). Exercise limitation was associated with the FAs' FEV(1) (r = 0.33; p = 0.003). The Dco increased less with exercise in those with abnormal resting Dco (mean±SEM: 1.36±0.16 vs. 1.90±0.16 ml/min/mmHg per 20% increase in predicted watts; p = 0.020), and amongst all FAs, the increase with exercise seemed to be incrementally lower in those with lower resting Dco. Exercise-induced increase in Qc was not different in the two groups. However, the FAs with abnormal resting Dco had less augmentation of their Dco with increase in Qc during exercise (mean±SEM: 0.93±0.06 vs. 1.47±0.09 ml/min/mmHg per L/min; p<0.0001). The Dco during exercise was inversely associated with years of exposure to SHS in those FAs with ≥10 years of pre-ban experience (r = -0.32; p = 0.032). CONCLUSIONS: This cohort of never-smoking FAs with SHS exposure showed exercise limitation based on their resting Dco. Those with lower resting Dco had reduced pulmonary capillary recruitment. Exposure to SHS in the aircraft cabin seemed to be a predictor for lower Dco during exercise

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

NFAT5 Is Activated by Hypoxia: Role in Ischemia and Reperfusion in the Rat Kidney

The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10–18 mmHg); however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO2) on NFAT5 activity. We found that 1) Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2) Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3) The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O2. 4) At 2.5% of O2, the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5) siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6) siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7) NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla) from rats subjected to an experimental model of ischemia and reperfusion (I/R). 7) Experimental I/R increased the NFAT5-target gene aldose reductase (AR). 8) NFAT5 activators (ATM and PI3K) were induced in vitro (HEK293 cells) and in vivo (I/R kidneys) with the same timing of NFAT5. 8) Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage

Use of cDNA Tiling Arrays for Identifying Protein Interactions Selected by In Vitro Display Technologies

In vitro display technologies such as mRNA display are powerful screening tools for protein interaction analysis, but the final cloning and sequencing processes represent a bottleneck, resulting in many false negatives. Here we describe an application of tiling array technology to identify specifically binding proteins selected with the in vitro virus (IVV) mRNA display technology. We constructed transcription-factor tiling (TFT) arrays containing ∼1,600 open reading frame sequences of known and predicted mouse transcription-regulatory factors (334,372 oligonucleotides, 50-mer in length) to analyze cDNA fragments from mRNA-display screening for Jun-associated proteins. The use of the TFT arrays greatly increased the coverage of known Jun-interactors to 28% (from 14% with the cloning and sequencing approach), without reducing the accuracy (∼75%). This method could detect even targets with extremely low expression levels (less than a single mRNA copy per cell in whole brain tissue). This highly sensitive and reliable method should be useful for high-throughput protein interaction analysis on a genome-wide scale

Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run

We summarize the sensitivity achieved by the LIGO and Virgo gravitational wave detectors for compact binary coalescence (CBC) searches during LIGO's fifth science run and Virgo's first science run. We present noise spectral density curves for each of the four detectors that operated during these science runs which are representative of the typical performance achieved by the detectors for CBC searches. These spectra are intended for release to the public as a summary of detector performance for CBC searches during these science runs.Comment: 12 pages, 5 figure