Ultra-Short Pulse Laser Cleaning of Contaminated Pleistocene Bone: A Comprehensive Study on the Influence of Pulse Duration and Wavelength

The impact of wavelength and pulse duration in laser cleaning of hard blackish contaminants crust from archaeologically significant Pleistocene bone is investigated in this research. The objective is to determine the practical cleaning procedures and identify adequate laser parameters for cleaning archaeological bone from Sima de los Huesos (Spain) based on conservation and restoration perspectives. Bone surface cleaning was performed utilizing two Q-switched Nd:YAG lasers: sub-nanosecond pulsed lasers with emission wavelengths at 355 nm and 1064 nm, respectively, and a Yb:KGW femtosecond pulsed laser with an emission wavelength in the third harmonic at 343 nm. In all experiments, the laser beam scanning mode was applied to measure cleaning efficiency in removing contaminants and degradation products while assessing the underlying substrate surface damage. Several properties, including wavelength-dependent absorption, pulse repetition rate, and thermal properties of the material, are analyzed when evaluating the ability of these lasers to boost the cleaning efficiency of the deteriorated bone surface. Bone surface morphology and composition were studied and compared before and after laser irradiation, using Optical Microscopy, Scanning Electron Microscopy with Energy Dispersive X-ray Spectrometry (SEM-EDS), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS) characterization methods. The results indicate that 238-femtosecond UV laser irradiation with 2.37 TWcm−2 is significantly safer and more efficient toward surface contaminant desorption than sub-nanosecond laser irradiation. The results herein presented suggest that these types of fs lasers may be considered for realistic laser conservation of valuable historic and archaeological museum artifacts

Small and large intestine express a truncated Dab1 isoform that assembles in cell-cell junctions and co-localizes with proteins involved in endocytosis

Disabled-1 (Dab1) is an essential intracellular adaptor protein in the reelin pathway. Our previous studies in mice intestine showed that Dab1 transmits the reelin signal to cytosolic signalling pathways. Here, we determine the Dab1 isoform expressed in rodent small and large intestine, its subcellular location and co-localization with clathrin, caveolin-1 and N-Wasp. PCR and sequencing analysis reveal that rodent small and large intestine express a Dab1 isoform that misses three (Y198, Y200and Y220) of the five tyrosine phosphorylation sites present in brain Dab1 isoform (canonical) and contains nuclear localization and export signals. Western blot assays show that both, crypts, which shelter progenitor cells, and enterocytes express the same Dab1 isoform, suggesting that epithelial cell differentiation does not regulate intestinal generation of alternatively spliced Dab1 variants. They also reveal that the canonical and the intestinal Dab1 isoforms differ in their total degree of phosphorylation. Immunostaining assays show that in enterocytes Dab1 localizes at the apical and lateral membranes, apical vesicles, close to adherens junctions and desmosomes, as well as in the nucleus; co-localizes with clathrin and with N-Wasp but not with caveolin-1, and in Caco-2 cells Dab1 localizes at cell-to-cell junctions by a Ca2+-dependent process. In conclusion, the results indicate that in rodent intestine a truncated Dab1 variant transmits the reelin signal and may play a role in clathrin-mediated apical endocytosis and in the control of cell-to-cell junctions assembly. A function of intestinal Dab1 variant as a nucleocytoplasmic shuttling protein is also inferred from its sequence and nuclear location

Ultrashort pulsed Femtosecond UV laser for selective cleaning of significant Cretaceous flints

This work reports on studies aimed to evaluate the utilization of ultrashort 238 fs (fs) pulsed UV laser emission at 343 nm for eliminating colored crusts and surface deposits on significant Cretaceous flint surfaces, in an attempt to safeguard its aesthetic appearance and archaeological value. The results indicate that fs UV lasers may be an ideal, non-contact tool for selective surface cleaning of sensitive archaeological artefacts, since they enable contaminant desorption while avoiding photothermal damage

Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

Effectiveness of Oral Nutritional Supplementation for Older Women after a Fracture: Rationale, Design and Study of the Feasibility of a Randomized Controlled Study

<p>Abstract</p> <p>Background</p> <p>Malnutrition is a problem for many older people recovering from a hip and other major fractures. Oral supplementation with high calorie high protein nutrients is a simple intervention that may help older people with fractures to improve their recovery in terms of rehabilitation time, length of hospital stay and mortality. This paper reports a pilot study to test the feasibility of a trial initiated in a hospital setting with an oral supplement to older people with recent fractures.</p> <p>Method</p> <p>A randomized controlled trial with 44 undernourished participants admitted to a hospital following a fracture. The intervention group (n = 23) received a high calorie high protein supplement for forty days in addition to their diet of choice. The control group (n = 21) received high protein milk during their hospital stay in addition to their diet of choice and their usual diet when discharged from hospital.</p> <p>Results</p> <p>All participants were women and their mean age was 85.3 (± 6.1) years. Twenty nine (65%) participants had a hip fracture. At baseline no differences were measured between the two groups regarding their nutritional status, their cognitive ability or their abilities in activities of daily living. There were no significant differences between the intervention and control group with reference to nutritional or functional parameters at 40 day and 4 month follow-ups. Median length of stay in hospital was 18.0 days, with 12 participants being readmitted for a median of 7.0 days.</p> <p>Conclusion</p> <p>It is feasible to perform a randomised trial in a hospital and community setting to test the effect of an oral high energy high protein supplement for older people. Due to the limited number of participants and incomplete adherence with use of the supplements no conclusion can be drawn about the efficacy or effectiveness of this intervention.</p

Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity

Low serum 25 hydroxyvitamin D3 (vitamin D3) is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in obesity and type II diabetes mellitus (TIIDM). Vitamin D3 insufficiency has been linked to obesity, whether obesity is assessed by body mass index (BMI) or waist circumference (waist). Central obesity, using waist as the surrogate, is associated with the metabolic syndrome (MetSyn), insulin resistance, TIIDM and atherosclerotic cardiovascular disease (CVD). We tested how vitamin D3 was related to measures of fat mass, MetSyn markers, haemoglobin A1c (HbA1c) and MetSyn in a cross-sectional sample of 250 overweight and obese adults of different ethnicities. There were modest inverse associations of vitamin D3 with body weight (weight) (r = -0.21, p = 0.0009), BMI (r = -0.18, p = 0.005), waist (r = -0.14, p = 0.03), [but not body fat % (r = -0.08, p = 0.24)], and HbA1c (r = -0.16, p = 0.01). Multivariable regression carried out separately for BMI and waist showed a decrease of 0.74 nmol/L (p = 0.002) in vitamin D3 per 1 kg/m2 increase in BMI and a decrease of 0.29 nmol/L (p = 0.01) per 1 cm increase in waist, with each explaining approximately 3% of the variation in vitamin D3 over and above gender, age, ethnicity and season

The Impact of Combination Antiretroviral Therapy and its Interruption on Anxiety, Stress, Depression and Quality of Life in Thai Patients

OBJECTIVE: Investigation on anxiety, stress, depression, and quality of life (QoL) within STACCATO, a randomised trial of two treatment strategies: CD4 guided scheduled treatment interruption (STI) compared to continuous treatment (CT). PARTICIPANTS: Thai patients with HIV-infection enrolled in the STACCATO trial. METHODS: Anxiety, depression assessed by the questionnaires Hospital Anxiety and Depression Scale (HADS) and DASS, stress assessed by the Depression Anxiety Stress Scale (DASS), and QoL evaluated by the HIV Medical Outcome Study (MOS-HIV) questionnaires. Answers to questionnaires were evaluated at 4 time-points: baseline, 24 weeks, 48 weeks and at the end of STACCATO. RESULTS: A total of 251 patients answered the HADS/DASS and 241 answered the MOS-HIV of the 379 Thai patients enrolled into STACCATO (66.2 and 63.6% respectively). At baseline 16.3% and 7.2% of patients reported anxiety and depression using HADS scale. Using the DASS scale, 35.1% reported mild to moderate and 9.6% reported severe anxiety; 8.8% reported mild to moderate and 2.0% reported severe depression; 42.6% reported mild to moderate and 4.8% reported severe stress. We showed a significant improvement of the MHS across time (p=0.001), but no difference between arms (p=0.17). The summarized physical health status score (PHS) did not change during the trial (p=0.15) nor between arm (p=0.45). There was no change of MHS or PHS in the STI arm, taking into account the number of STI cycle (p=0.30 and 0.57) but MHS significant increased across time-points (p=0.007). CONCLUSION: Antiretroviral therapy improved mental health and QOL, irrespective of the treatment strategy

Phenology of Scramble Polygyny in a Wild Population of Chrysolemid Beetles: The Opportunity for and the Strength of Sexual Selection

Recent debate has highlighted the importance of estimating both the strength of sexual selection on phenotypic traits, and the opportunity for sexual selection. We describe seasonal fluctuations in mating dynamics of Leptinotarsa undecimlineata (Coleoptera: Chrysomelidae). We compared several estimates of the opportunity for, and the strength of, sexual selection and male precopulatory competition over the reproductive season. First, using a null model, we suggest that the ratio between observed values of the opportunity for sexual selections and their expected value under random mating results in unbiased estimates of the actual nonrandom mating behavior of the population. Second, we found that estimates for the whole reproductive season often misrepresent the actual value at any given time period. Third, mating differentials on male size and mobility, frequency of male fighting and three estimates of the opportunity for sexual selection provide contrasting but complementary information. More intense sexual selection associated to male mobility, but not to male size, was observed in periods with high opportunity for sexual selection and high frequency of male fights. Fourth, based on parameters of spatial and temporal aggregation of female receptivity, we describe the mating system of L. undecimlineata as a scramble mating polygyny in which the opportunity for sexual selection varies widely throughout the season, but the strength of sexual selection on male size remains fairly weak, while male mobility inversely covaries with mating success. We suggest that different estimates for the opportunity for, and intensity of, sexual selection should be applied in order to discriminate how different behavioral and demographic factors shape the reproductive dynamic of populations

Role of Plant-Specific N-Terminal Domain of Maize CK2β1 Subunit in CK2β Functions and Holoenzyme Regulation

Protein kinase CK2 is a highly pleiotropic Ser/Thr kinase ubiquituous in eukaryotic organisms. CK2 is organized as a heterotetrameric enzyme composed of two types of subunits: the catalytic (CK2α) and the regulatory (CK2β). The CK2β subunits enhance the stability, activity and specificity of the holoenzyme, but they can also perform functions independently of the CK2 tetramer. CK2β regulatory subunits in plants differ from their animal or yeast counterparts, since they present an additional specific N-terminal extension of about 90 aminoacids that shares no homology with any previously characterized functional domain. Sequence analysis of the N-terminal domain of land plant CK2β subunit sequences reveals its arrangement through short, conserved motifs, some of them including CK2 autophosphorylation sites. By using maize CK2β1 and a deleted version (ΔNCK2β1) lacking the N-terminal domain, we have demonstrated that CK2β1 is autophosphorylated within the N-terminal domain. Moreover, the holoenzyme composed with CK2α1/ΔNCK2β1 is able to phosphorylate different substrates more efficiently than CK2α1/CK2β1 or CK2α alone. Transient overexpression of CK2β1 and ΔNCK2β1 fused to GFP in different plant systems show that the presence of N-terminal domain enhances aggregation in nuclear speckles and stabilizes the protein against proteasome degradation. Finally, bimolecular fluorescence complementation (BiFC) assays show the nuclear and cytoplasmic location of the plant CK2 holoenzyme, in contrast to the individual CK2α/β subunits mainly observed in the nucleus. All together, our results support the hypothesis that the plant-specific N-terminal domain of CK2β subunits is involved in the down-regulation of the CK2 holoenzyme activity and in the stabilization of CK2β1 protein. In summary, the whole amount of data shown in this work suggests that this domain was acquired by plants for regulatory purposes

Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation

Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors.The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes.The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response