Mitotic spindle positioning protein (MISP) preferentially binds to aged F-actin.

Actin bundling proteins crosslink filaments into polarized structures that shape and support membrane protrusions including filopodia, microvilli, and stereocilia. In the case of epithelial microvilli, mitotic spindle positioning protein (MISP) is an actin bundler that localizes specifically to the basal rootlets, where the pointed ends of core bundle filaments converge. Previous studies established that MISP is prevented from binding more distal segments of the core bundle by competition with other actin-binding proteins. Yet whether MISP holds a preference for binding directly to rootlet actin remains an open question. By immunostaining native intestinal tissue sections, we found that microvillar rootlets are decorated with the severing protein, cofilin, suggesting high levels of ADP-actin in these structures. Using total internal reflection fluorescence microscopy assays, we also found that purified MISP exhibits a binding preference for ADP- versus ADP-Pi-actin-containing filaments. Consistent with this, assays with actively growing actin filaments revealed that MISP binds at or near their pointed ends. Moreover, although substrate attached MISP assembles filament bundles in parallel and antiparallel configurations, in solution MISP assembles parallel bundles consisting of multiple filaments exhibiting uniform polarity. These discoveries highlight nucleotide state sensing as a mechanism for sorting actin bundlers along filaments and driving their accumulation near filament ends. Such localized binding might drive parallel bundle formation and/or locally modulate bundle mechanical properties in microvilli and related protrusions.

Giant valley-Zeeman coupling in the surface layer of an intercalated transition metal dichalcogenide.

Spin-valley locking is ubiquitous among transition metal dichalcogenides with local or global inversion asymmetry, in turn stabilizing properties such as Ising superconductivity, and opening routes towards 'valleytronics'. The underlying valley-spin splitting is set by spin-orbit coupling but can be tuned via the application of external magnetic fields or through proximity coupling. However, only modest changes have been realized to date. Here, we investigate the electronic structure of the V-intercalated transition metal dichalcogenide V1/3NbS2 using microscopic-area spatially resolved and angle-resolved photoemission spectroscopy. Our measurements and corresponding density functional theory calculations reveal that the bulk magnetic order induces a giant valley-selective Ising coupling exceeding 50 meV in the surface NbS2 layer, equivalent to application of a ~250 T magnetic field. This energy scale is of comparable magnitude to the intrinsic spin-orbit splittings, and indicates how coupling of local magnetic moments to itinerant states of a transition metal dichalcogenide monolayer provides a powerful route to controlling their valley-spin splittings.

Genetic regulation of the ompX porin of Salmonella Typhimurium in response to hydrogen peroxide stress.

BACKGROUND: Salmonella Typhimurium is a Gram-negative pathogen that causes a systemic disease in mice resembling typhoid fever. During its infective cycle, S. Typhimurium is phagocytized by macrophages and proliferates inside a Salmonella-containing vacuole where Salmonella is exposed and survives oxidative stress induced by H2O2 through modulation of gene expression. After exposure of Salmonella to H2O2, the expression of the porin-encoding gene ompX increases, as previously shown by microarray analysis. Expression of ompX mRNA is regulated at a post-transcriptional level by MicA and CyaR sRNAs in aerobiosis. In addition, sequence analysis predicts a site for OxyS sRNA in ompX mRNA. RESULTS: In this work we sought to evaluate the transcriptional and post-transcriptional regulation of ompX under H2O2 stress. We demonstrate that ompX expression is induced at the transcriptional level in S. Typhimurium under such conditions. Unexpectedly, an increase in ompX gene transcript and promoter activity after challenges with H2O2 does not translate into increased protein levels in the wild-type strain, suggesting that ompX mRNA is also regulated at a post-transcriptional level, at least under oxidative stress. In silico gene sequence analysis predicted that sRNAs CyaR, MicA, and OxyS could regulate ompX mRNA levels. Using rifampicin to inhibit mRNA expression, we show that the sRNAs (MicA, CyaR and OxyS) and the sRNA:mRNA chaperone Hfq positively modulate ompX mRNA levels under H2O2-induced stress in Salmonella during the exponential growth phase in Lennox broth. CONCLUSIONS: Our results demonstrate that ompX mRNA is regulated in response to H2O2 by the sRNAs CyaR, MicA and OxyS is Salmonella Typhimurium.

Brachial-ankle pulse wave velocity with a custom device. / Velocidad de onda de pulso brazo-tobillo con un dispositivo propio.

BACKGROUND AND OBJECTIVES: The brachial-ankle pulse wave velocity (baPWV) is one of the most widely used arterial stiffness variables for assessing vascular risk. The abiPWV is a device that calculates various PWVs and the blood pressure ankle-brachial index (ABI). The device can also determine baPWV. The aim of this study was to calculate the baPWV with abiPWV, validate it with a reference device (VaSera) and study its clinical usefulness. PATIENTS AND METHODS: We studied 113 patients (mean age, 53±12years), 59 (52%) of whom were women, and 10 (8.8%) of whom had a previous cardiovascular event. The participants were classified according to cardiovascular risk factors (CRFs) into groupI (none), groupII (1 or 2 CRFs) and groupIII (3 or more CRFs). The patients with a previous cardiovascular event were included in groupIII. All participants had their baPWV measured with abiPWV and VaSera. RESULTS: The baPWV correlation between the 2 devices was r=0.93 (P<.001), and the percentage error calculated with the Bland-Altman analysis was 4.5%. The baPWV measured with abiPWV (in m/s) was as follows: groupI, 10.5±1.6; groupII, 13.8±2.9 (P<.001 when compared with groupI); and groupIII, 14.1±2.7 (P<.001 when compared with groupI). There were no differences between groupsII and III. The results with VaSera were comparable to those of abiPWV. CONCLUSIONS: Measuring baPWV with the abiPWV is safe and has a similar clinical utility to that of VaSera. Incorporating this function into the options of abiPWV makes it a complete device for assessing arterial stiffness.

Synthesis of Ruthenium-Doped TiO2 Nanotube Arrays for the Photocatalytic Degradation of Terasil Blue Dye.

The oxidation of terasil blue dye (TB) has been achieved by photocatalysis under UV light using well organized nanotubes of Ti/TiO2 doped with ruthenium (Ru/Ti/TiO2). Ru/Ti/TiO2 were fabricated by Ti anodization followed by impregnation with 0.04, 0.08 and 0.16 wt% of RuCl3 · xH2O or KRuO4 as precursor salts. Ti foil anodization was carried out in non-aqueous solutions and in aqueous solutions at pH 7 and pH 12.6. Scanning electron microscopy analyses revealed a morphology of well-defined, organized nanotubes of Ti/TiO2 and Ru/Ti/TiO2. The ruthenium was evenly distributed over Ti/TiO2 surface. Cluster formation was also observed for 0.16 wt% Ru loading. The X-ray diffraction spectra showed anatase and rutile phase in pure Ti/TiO2 and Ru/Ti/TiO2 nanotubes. Therefore, ruthenium doping did not modify the crystalline phase of Ti/TiO2. Raman spectra did not reveal the rutile phase of TiO2 in the composites which is attributed to the laser characteristics used. The optical band gap energies of the Ti/TiO2 and Ru/Ti/TiO2 nanotube arrays showed that ruthenium-doping on Ti/TiO2 had slight effect on the band-gap energy. A decrease in the band gap energy of pure Ti/TiO2 (Eg 2.88 eV) was observed by Ru loading of 0.04 wt% in the Ti/TiO2 nanotube arrays (Eg 2.60 eV). The kinetic rate constant of the photocatalytic oxidation of TB, using 0.08 wt% Ru load, was 1.56 and 1.39 times of that on Ti/TiO2 composite (0.01 min-1) synthetized at pH 12.6 impregnated in RuCl3 (0.0156 min-1) and KRuO4 (0.0139 min-1) solutions, respectively. Nevertheless, the highest rate constant value of TB degradation (87.8%) was 0.0172 min-1 using 0.16 wt% Ru loading on Ti/TiO2 composite synthetized at pH 7 impregnated in RuCl3; this represents 1.15 times of that on Ti/TiO2 composite (0.0150 min-1; 81.4% color removal) synthetized under the same conditions.

Energetic valorization of MSW compost valorization by selecting the maturity conditions.

MSW compost valorization under combustion, at two different composting process conditions, have been studied by thermogravimetric analysis (TGA). The composting operating parameters such as aeration and moisture affect the biodegradability of compost and results of the combustion (different gross heating values for each reactors). The obtained TGA showed that maximum weight loss for 10-12% (245-247 °C), 32-34% (407-411 °C) and 44-46% (760-769 °C) in correspondence to hemicellulose, cellulose and lignin-humic-fulvic acids decomposition for each reactor are observed. Obtained valued in kinetic study (Flynn-Wall-Ozawa method) results in suitable coefficients of determination. In that form, to establish the assumption that combustion of compost under a first-order reaction may be appropriate. Moreover, in both reactors, the conversion rate increased and the activation energy decreased with composting time is found. The maximum gross heating value versus minimum activation energy (for α = 0.25 and α = 0.5) corresponds to final composts and under aeration of 0.050 and 0.175 Lair kg-1 d-1 and moisture of 40% and 55% for R1 and R2 reactors respectively. For MSW, under proper conditions, composting could be used as a suitable biodrying process, stabilizing and concentrating the heating value.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Respiratory tract infection caused by Mycobacterium bovis in a black swan (Cygnus atratus).

A 3-year-old male black swan (Cygnus atratus), belonging to a private collection, died suddenly and was subjected to post mortem examination. At necropsy, caseous exudate was observed in the lungs and air sacs; granulomatous lesions characterized by epithelioid macrophages and abundant mycobacteria were observed microscopically. Avian tuberculosis associated with Mycobacterium bovis was confirmed by bacteriologic isolation, biochemical tests and molecular methods. The organism was identified as spoligotype SB0140, which is frequently found in cattle and people in North America. In this case, interspecies transmission could have been the source of infection because the swan cohabited with cattle.

Deficit of vitamin D in pregnancy and growth and overweight in the offspring.

BACKGROUND: Maternal vitamin D status during fetal development may influence offspring growth and risk of obesity; however, evidence in humans is limited. OBJECTIVE: To investigate whether maternal circulating 25-hydroxyvitamin D3 (25(OH)D3) concentration in pregnancy is associated with offspring prenatal and postnatal growth and overweight. METHODS: Plasma 25(OH)D3 concentration was measured in pregnant women (median weeks of gestation 14.0, range 13.0-15.0) from the INMA (INfancia y Medio Ambiente) cohort (Spain, 2003-2008) (n = 2358). Offspring femur length (FL), biparietal diameter (BPD), abdominal circumference (AC) and estimated fetal weight (EFW) were evaluated at 12, 20 and 34 weeks of gestation by ultrasound examinations. Fetal overweight was defined either as AC or as EFW ⩾ 90th percentile. Child's anthropometry was recorded at ages 1 and 4 years. Rapid growth was defined as a weight gain z-score of >0.67 from birth to ages 6 months and 1 year. Age- and sex-specific z-scores for body mass index (BMI) were calculated at ages 1 and 4 years (World Health Organization referent); infant's overweight was defined as a BMI z-score ⩾ 85th percentile. RESULTS: We found no association of maternal 25(OH)D3 concentration with FL and a weak inverse association with BPD at 34 weeks. Maternal deficit of 25(OH)D3 (<20 ng ml(-1)) was associated with increased risk of fetal overweight defined as AC ⩾ 90th percentile (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.01-2.21; P = 0.041) or either as EFW ⩾ 90th percentile (OR = 1.47, 95% CI: 1.00-2.16; P = 0.046). No significant associations were found with rapid growth. Deficit of 25(OH)D3 in pregnancy was associated with an increased risk of overweight in offspring at age 1 year (OR = 1.42, 95% CI: 1.02-1.97; P = 0.039); however, the association was attenuated at age 4 years (OR = 1.19, 95% CI: 0.83-1.72; P = 0.341). CONCLUSIONS: Vitamin D deficiency in pregnancy may increase the risk of prenatal and early postnatal overweight in offspring. Clinical trials are warranted to determine the role of vitamin D in the early origins of obesity.

Associations of maternal circulating 25-hydroxyvitamin D3 concentration with pregnancy and birth outcomes.

OBJECTIVE: To investigate the association of maternal circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration with pregnancy and birth outcomes. DESIGN: Prospective cohort study. SETTING: Four geographical areas of Spain, 2003-2008. POPULATION: Of 2382 mother-child pairs participating in the INfancia y Medio Ambiente (INMA) Project. METHODS: Maternal circulating 25(OH)D3 concentration was measured in pregnancy (mean [SD] 13.5 [2.2] weeks of gestation). We tested associations of maternal 25(OH)D3 concentration with pregnancy and birth outcomes. MAIN OUTCOME MEASURES: Gestational diabetes mellitus (GDM), preterm delivery, caesarean section, fetal growth restriction (FGR) and small-for-gestational age (SGA), anthropometric birth outcomes including weight, length and head circumference (HC). RESULTS: Overall, 31.8% and 19.7% of women had vitamin D insufficiency [25(OH)D3 20-29.99 ng/ml] and deficiency [25(OH)D3 < 20 ng/ml], respectively. After adjustment, there was no association between maternal 25(OH)D3 concentration and risk of GDM or preterm delivery. Women with sufficient vitamin D [25(OH)D3 ≥ 30 ng/ml] had a decreased risk of caesarean section by obstructed labour compared with women with vitamin D deficiency [relative risk (RR) = 0.60, 95% CI 0.37, 0.97). Offspring of mothers with higher circulating 25(OH)D3 concentration tended to have smaller HC [coefficient (SE) per doubling concentration of 25(OH)D3, -0.10 (0.05), P = 0.038]. No significant associations were found for other birth outcomes. CONCLUSION: This study did not find any evidence of an association between vitamin D status in pregnancy and GDM, preterm delivery, FGR, SGA and anthropometric birth outcomes. Results suggest that sufficient circulating vitamin D concentration [25(OH)D3 ≥ 30 ng/ml] in pregnancy may reduce the risk of caesarean section by obstructed labour.

Pre- and postnatal exposure to tobacco smoke and respiratory outcomes during the first year.

The different role of prenatal and postnatal exposure to tobacco smoke in respiratory outcomes in infants has not yet been clearly established. Our objective is to assess the effects of these exposures on the risk of respiratory outcomes during the first year of life of infants from a Spanish multicenter cohort study. A total of 2506 women were monitored until delivery. About 2039 infants made up the final population. The outcomes were caused by the occurrence of the following: otitis, cough persisting for more than 3 weeks, lower respiratory tract symptoms (wheezing or chestiness), and lower respiratory tract infections (bronchitis, bronchiolitis, or pneumonia). The relationship between prenatal and postnatal exposure and health outcomes was explored using logistic regression analysis. Maternal smoking during pregnancy increased the odds for wheezing (OR: 1.41, 95% CI: 0.99-2.01) and chestiness (OR: 1.46, 95% CI: 1.03-2.01). Postnatal exposure from fathers was associated with otitis (OR: 1.25, 95% CI: 1.01-1.54). Passive exposure at work of non-smoking mothers during pregnancy was related to cough (OR: 1.62, 95% CI: 1.05-2.51). Exposure to tobacco smoke was related to a higher risk of experiencing respiratory outcomes in young infants. Prenatal exposure was that most clearly associated with the respiratory outcomes analyzed.

The experiences of participating in winter among youths with a physical disability compared with their typically developing peers.

BACKGROUND: Having a physical disability and using a wheelchair can create difficulties in navigating the physical and built environment, especially during winter when snow and ice become problematic. Little is known about the experiences of winter among youth who use an assistive mobility device. This study aimed to understand how youth with a physical disability experience winter, compared with typically developing peers. METHODS: A purposive sample of 25 youths (13 with a physical disability; 12 typically developing) completed a 2-week weather journal and photographs in two Canadian cities during winter. These data were used to guide semi-structured interviews with participants. RESULTS: Youths with disabilities experienced many similar challenges in winter, such as health and safety concerns and accessibility issues, compared with typically developing youth - but to a greater extent. Youths with disabilities reported more challenges going outdoors during winter and negative psychosocial impacts, including loneliness and increased dependence, compared with peers without a disability. They also, however, described developing several adaptive strategies to cope with these challenges. CONCLUSIONS: There is a strong need to remove physical and environmental barriers to facilitate the participation and inclusion of youth with disabilities in winter.

Perinatal factors associated with the development of cow's milk protein allergy.

UNLABELLED: The prevalence of cow's milk protein allergy (CMPA) has increased in recent years, and is associated with antimicrobial use during the perinatal period, prematurity, the type of childbirth, and the decrease in breastfeeding. The aim of this study was to analyze whether there is any association between these factors and the development of CMPA. MATERIAL AND METHODS: A retrospective, comparative, cross-sectional, observational study was conducted by reviewing the case records of 101 children diagnosed with CMPA and seen at the Department of Gastroenterology and Nutrition of the Instituto Nacional de Pediatría within the time frame of January 2012 and August 2013. The following variables were included: age, sex, weeks of gestation, history of maternal infection and antimicrobial use during the pregnancy, type of delivery, and feeding with human milk, and its duration. Likewise, the case records of 90 children were reviewed as a control group on not having CMPA or any other allergy. The chi-square test was used for proportions, and the Mann-Whitney U test was used for comparing means in the statistical analysis. RESULTS: The factors associated with CMPA were the use of antimicrobials during gestation and breastfeeding duration in months. Both factors were statistically significant (P<.001). No association was found between CMPA and gestational age or type of delivery. CONCLUSIONS: The statistically significant associated factors were breastfeeding duration and the use of antimicrobials during the gestational stage. These results underline the necessity for prospective studies.

Oral administration of cobalt acetate alters milk fatty acid composition, consistent with an inhibition of stearoyl-coenzyme A desaturase in lactating ewes.

Previous investigations have shown that cobalt (Co) modifies milk fat composition in cattle, consistent with an inhibition of stearoyl-coenzyme A desaturase (SCD) activity, but it remains unclear whether other ruminant species are also affected. The present study examined the effects of oral administration of Co acetate on intake, rumen function, and milk production and fatty acid (FA) composition in sheep. Twenty lactating Assaf ewes were allocated into 1 of 4 groups and used in a continuous randomized block design that involved a 15-d adaptation, a 6-d treatment, and a 10-d posttreatment period. During the treatment period, animals received an oral drench supplying 0 (control), 3 (Co3), 6 (Co6), and 9 (Co9) mg of Co/kg of BW per day, administered in 3 equal doses at 8-h intervals. Cobalt acetate had no influence on intake or milk fat and protein concentrations, whereas treatments Co6 and Co9 tended to lower milk yield. Results on rumen parameters showed no effects on rumen fermentation, FA composition, or bacterial community structure. Administration of Co acetate decreased milk concentrations of FA containing a cis-9 double bond and SCD product:substrate ratios, consistent with an inhibition of SCD activity in the ovine mammary gland. Temporal changes in milk fat composition indicated that the effects of treatments were evident within 3d of dosing, with further changes being apparent after 6d and reverting to pretreatment values by d 6 after administration. Effect on milk FA composition did not differ substantially in response to incremental doses of Co acetate. On average, Co decreased milk cis-9 10:1/10:0, cis-9 12:1/12:0, cis-9 14:1/14:0, cis-9 16:1/16:0, cis-9 17:1/17:0, cis-9 18:1/18:0, and cis-9,trans-11 18:2/trans-11 18:1 concentration ratios by 30, 32, 38, 33, 21, 24, and 25%, respectively. Changes in milk fat cis-9 10:1, cis-9 12:1, and cis-9 14:1 concentrations to Co treatment indicated that 51% of cis-9 18:1 and cis-9,trans-11 18:2 secreted in milk originated from Δ(9)-desaturation. In conclusion, results demonstrated the potential of oral Co administration for the estimation of endogenous synthesis of FA containing a cis-9 double bond in the mammary gland of lactating ruminants. Indirect comparisons suggest that the effects of Co differ between sheep and cattle.

Influence of histological degree of seminiferous tubular degeneration and stage of seminiferous cycle on the proliferation of spermatogonia in aged Syrian hamster (Mesocricetus auratus).

The ageing testis is associated with germ loss in the seminiferous epithelium and a decrease in spermatogonia proliferation. In this work, we study whether the stages of the seminiferous epithelium cycle and/or the degree of histological tubular degeneration resulting from ageing is related with this decrease in spermatogonia proliferation. Eleven hamsters were used, five aged 6 months and six aged 24 months. In both groups, the proliferative activity was studied by BrdU immunostaining. The number of BrdU-positive and BrdU-negative cells was measured, providing the overall proliferation index in adult and aged testes. The mean number of BrdU-positive cells was also determined for each degree of histological degeneration of seminiferous epithelium, and a spermatogonia proliferation index was obtained for each stage of the seminiferous cycle. Ageing caused an overall decrease in the BrdU-positive cell percentage and a decrease in the number of BrdU-positive cells in the tubular sections with hypospermatogenesis, the sloughing of germ cells and maturation arrest, these changes being similar in both young and old animals. The spermatogonia proliferation index was only seen to be significantly lower in ageing hamster in stages VII-VIII of the seminiferous epithelium cycle. In conclusion, the overall decrease in proliferation observed in aged seminiferous epithelium is correlated with an increase in the number of degenerated sections of the seminiferous tubules, and this decrease is a phenomenon which occurs in specific stages of the seminiferous cycle.

Microbial and chemical composition of liquid-associated bacteria in goats' rumen and fermenters.

This study was undertaken to investigate the relationship between chemical composition and microbial profile of rumen liquid-associated bacteria (LAB) in vivo (Murciano-Granadina goats) and in a rumen simulation system (single-flow continuous-culture fermenters). To achieve this aim, analyses of purine bases along with some molecular techniques (quantitative PCR to assess abundance and DGGE to identify biodiversity and bacterial profile) were carried out. A control diet (AHC) based on alfalfa hay (AH) and concentrate (C) in a 1:1 ratio and two experimental diets (AHCBI and AHCBII), in which concentrate was partially replaced with multinutrient blocks, were used. Diets AHCBI and AHCBII included multinutrient blocks differing in the relative amount of two-stage olive cake and the source of protein (sunflower meal vs. fava beans). We aimed to investigate the effect of these blocks on rumen microbiota to evaluate their potential as safe substitutes of cereal-based concentrates. Similar patterns of response to diet were found for chemical composition, microbial abundances and diversity in LAB isolated from goat's rumen and fermenters. Whereas bacterial density (log10 gene copies/g FM: 11.6 and 9.4 for bacteria and methanogens, respectively, in rumen) and diversity indexes (Shannon index: 3.6) were not affected by diet, DGGE analyses showed that bacterial community profile was affected. The cluster analysis suggested differences in bacterial profile between LAB pellets isolated from the rumen of goat and fermenters. A relationship between chemical composition and bacterial community composition in LAB pellets seems to exist. Changes in the former were reflected in the bacterial community profile. Further research is needed to clarify the relationship between chemical and microbial composition of ruminal bacterial pellets with diets of different quality.

Salivary gland developmental mechanics.

The salivary gland undergoes branching morphogenesis to elaborate into a tree-like structure with numerous saliva-secreting acinar units, all joined by a hierarchical ductal system. The expansive epithelial surface generated by branching morphogenesis serves as the structural basis for the efficient production and delivery of saliva. Here, we elucidate the process of salivary gland morphogenesis, emphasizing the role of mechanics. Structurally, the developing salivary gland is characterized by a stratified epithelium tightly encased by the basement membrane, which is in turn surrounded by a mesenchyme consisting of a dense network of interstitial matrix and mesenchymal cells. Diverse cell types and extracellular matrices bestow this developing organ with organized, yet spatially varied mechanical properties. For instance, the surface epithelial sheet of the bud is highly fluidic due to its high cell motility and weak cell-cell adhesion, rendering it highly pliable. In contrast, the inner core of the bud is more rigid, characterized by reduced cell motility and strong cell-cell adhesion, which likely provide structural support for the tissue. The interactions between the surface epithelial sheet and the inner core give rise to budding morphogenesis. Furthermore, the basement membrane and the mesenchyme offer mechanical constraints that could play a pivotal role in determining the higher-order architecture of a fully mature salivary gland.

Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours.

BACKGROUND: Cisplatin cures over 80% of testicular germ cell tumours (TGCTs), and nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. We explored the association between NER proteins and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) of patients with non-seminomatous (ns)-TGCTs. METHODS: The expression of ERCC1 and XPA and the presence of γH2AX were evaluated in cancer cell lines and in fresh ns-TGCTs. The ERCC1 protein was also determined in ns-TGCTs. The differences between CPS and non-CPS cell lines and patients were analysed by Student's t- or χ(2)-tests. The differences in OS were analysed using the log-rank test, and the hazard ratios (HRs) were calculated using the Cox model. RESULTS: High ERCC1 expression was observed in the non-CPS cells, and both ERCC1 and γH2AX expressions were augmented after cisplatin treatment. Increased ERCC1 expression was also identified in non-CPS patients. Neither polymorphism was associated with either CPS or OS. The presence of ERCC1 was associated with non-CPS (P=0.05) and adjusted in the prognosis groups. The HR in ERCC1-negative and non-CPS patients was >14.43, and in ERCC1-positive and non-CPS patients the HR was >11.86 (P<0.001). CONCLUSIONS: High levels of ERCC1 were associated with non-CPS, suggesting that ERCC1 could be used as a potential indicator of the response to cisplatin and prognosis in ns-TGCTs.