BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

Cerebrovascular reactivity (CVR) is a dynamic measure of the cerebral blood vessel response to vasoactive stimulus. Conventional CVR measures amplitude changes in the blood‐oxygenation‐level‐dependent (BOLD) signal per unit change in end‐tidal CO₂ (P_ETCO₂), effectively discarding potential timing information. This study proposes a deconvolution procedure to characterize CVR responses based on a vascular transfer function (VTF) that separates amplitude and timing CVR effects. We implemented the CVR‐VTF to primarily evaluate normal‐appearing white matter (WM) responses in those with a range of small vessel disease. Comparisons between simulations of P_ETCO₂ input models revealed that boxcar and ramp hypercapnia paradigms had the lowest relative deconvolution error. We used a T₂* BOLD‐MRI sequence on a 3 T MRI scanner, with a boxcar delivery model of CO₂, to test the CVR‐VTF approach in 18 healthy adults and three white matter hyperintensity (WMH) groups: 20 adults with moderate WMH, 12 adults with severe WMH, and 10 adults with genetic WMH (CADASIL). A subset of participants performed a second CVR session at a one‐year follow‐up. Conventional CVR, area under the curve of VTF (VTF‐AUC), and VTF time‐to‐peak (VTF‐TTP) were assessed in WM and grey matter (GM) at baseline and one‐year follow‐up. WMH groups had lower WM VTF‐AUC compared with the healthy group (p < 0.0001), whereas GM CVR did not differ between groups (p > 0.1). WM VTF‐TTP of the healthy group was less than that in the moderate WMH group (p = 0.016). Baseline VTF‐AUC was lower than follow‐up VTF‐AUC in WM (p = 0.013) and GM (p = 0.026). The intraclass correlation for VTF‐AUC in WM was 0.39 and coefficient of repeatability was 0.08 [%BOLD/mm Hg]. This study assessed CVR timing and amplitude information without applying model assumptions to the CVR response; this approach may be useful in the development of robust clinical biomarkers of CSVD.     

Time‐efficient measurement of multi‐phase arterial spin labeling MR signal in white matter

White matter (WM) perfusion has great potential as a physiological biomarker in many neurological diseases. Although it has been demonstrated previously that arterial spin labeling magnetic resonance imaging (ASL‐MRI) enables the detection of the perfusion‐weighted signal in most voxels in WM, studies of cerebral blood flow (CBF) in WM by ASL‐MRI are relatively scarce because of its particular challenges, such as significantly lower perfusion and longer arterial transit times relative to gray matter (GM). Recently, ASL with a spectroscopic readout has been proposed to enhance the sensitivity for the measurement of WM perfusion. However, this approach suffers from long acquisition times, especially when acquiring multi‐phase ASL datasets to improve CBF quantification. Furthermore, the potential increase in the signal‐to‐noise ratio (SNR) by spectroscopic readout compared with echo planar imaging (EPI) readout has not been proven experimentally. In this study, we propose the use of time‐encoded pseudo‐continuous ASL (te‐pCASL) with single‐voxel point‐resolved spectroscopy (PRESS) readout to quantify WM cerebral perfusion in a more time‐efficient manner. Results are compared with te‐pCASL with a conventional EPI readout for both WM and GM perfusion measurements. Perfusion measurements by te‐pCASL PRESS and conventional EPI showed no significant difference for quantitative WM CBF values (Student's t‐test, p = 0.19) or temporal SNR (p = 0.33 and p = 0.81 for GM and WM, respectively), whereas GM CBF values (p = 0.016) were higher using PRESS than EPI readout. WM CBF values were found to be 18.2 ± 7.6 mL/100 g/min (PRESS) and 12.5 ± 5.5 mL/100 g/min (EPI), whereas GM CBF values were found to be 77.1 ± 11.2 mL/100 g/min (PRESS) and 53.6 ± 9.6 mL/100 g/min (EPI). This study demonstrates the feasibility of te‐pCASL PRESS for the quantification of WM perfusion changes in a highly time‐efficient manner, but it does not result in improved temporal SNR, as does traditional te‐pCASL EPI, which remains the preferred option because of its flexibility in use.     

Errors in 1H‐MRS estimates of brain metabolite concentrations caused by failing to take into account tissue‐specific signal relaxation

Accurate measurement of brain metabolite concentrations with proton magnetic resonance spectroscopy (¹H‐MRS) can be problematic because of large voxels with mixed tissue composition, requiring adjustment for differing relaxation rates in each tissue if absolute concentration estimates are desired. Adjusting for tissue‐specific metabolite signal relaxation, however, also requires a knowledge of the relative concentrations of the metabolite in gray (GM) and white (WM) matter, which are not known a priori. Expressions for the estimation of the molality and molarity of brain metabolites with ¹H‐MRS are extended to account for tissue‐specific relaxation of the metabolite signals and examined under different assumptions with simulated and real data. Although the modified equations have two unknowns, and hence are unsolvable explicitly, they are nonetheless useful for the estimation of the effect of tissue‐specific metabolite relaxation rates on concentration estimates under a range of assumptions and experimental parameters using simulated and real data. In simulated data using reported GM and WM T₁ and T₂ times for N‐acetylaspartate (NAA) at 3 T and a hypothetical GM/WM NAA ratio, errors of 6.5–7.8% in concentrations resulted when TR = 1.5 s and TE = 0.144 s, but were reduced to less than 0.5% when TR = 6 s and TE = 0.006 s. In real data obtained at TR/TE = 1.5 s/0.04 s, the difference in the results (4%) was similar to that obtained with simulated data when assuming tissue‐specific relaxation times rather than GM–WM‐averaged times. Using the expressions introduced in this article, these results can be extrapolated to any metabolite or set of assumptions regarding tissue‐specific relaxation. Furthermore, although serving to bound the problem, this work underscores the challenge of correcting for relaxation effects, given that relaxation times are generally not known and impractical to measure in most studies. To minimize such effects, the data should be acquired with pulse sequence parameters that minimize the effect of signal relaxation.     

Synthesis and Characterization of Constitutional Isomeric Poly(amide‐ester)s from Adipoyl Chloride and 4‐(2‐Aminoethyl)phenol

Ordered [head‐to‐head (H‐H) or tail‐to‐tail (T‐T)] poly(amide‐ester) ( 6 a ) was prepared by polycondensation from adipoyl chloride ( 1 ) and N,N ′‐bis(4‐hydroxy phenethyl)adipamide ( 5 ), which was prepared from the selective acylation of 4‐(2‐aminoethyl)phenol ( 2 ) with N,N ′‐adipoylbis[benzoxazoline‐2‐thione] ( 4 ). And H‐T ordered poly(amide‐ester) ( 6 b ) was prepared by self‐polycondensation of 4‐carboxy‐N‐(4‐hydroxyphenethyl)‐adipamide ( 7 ) in the presence of DBOP. Random poly(amide‐ester) ( 6 c ) was synthesized by polymerization of 1 with 2 . The microstructure of the polymers obtained was investigated by ¹H and ¹³C NMR spectroscopy, and it was found that the polymers obtained had the expected ordered structure. Furthermore, DSC and WAXD results demonstrated that the constitutional regularity of polymers influenced their thermal properties and crystallinity.     

Synthesis and Photoinitiated Cationic Polymerization of Substituted 2‐Cyclopropyl‐4‐methylene‐1,3‐dioxolanes

The synthesis of substituted 2‐cyclopropyl‐4‐methylene‐1,3‐dioxolanes 6 a – c is described. Photoinitiated cationic polymerization at ambient temperatures in bulk and in solution was investigated using (η⁵‐2,4‐cyclopentadiene‐1‐yl)[1,2,3,4,5,6‐η (1‐(methylethyl) benzene)iron(II) hexafluorophosphate (Irgacure 261, I‐1 ) and ditolyliodonium hexafluoro‐phosphate ( I‐2 ). Upon irradiation a single ring‐opening polymerization occured within 4 min leading to polyether ketones 6 a – c with number average molecular weights M_w between 5 000 and 33 600 g/mol. No ring‐opening polymerization of the cyclopropane ring could be detected. A volume shrinkage of about 6.4% was found.     

Differential Age‐Related Effects on Visual‐ and Associative‐Based Semantic Encoding

This study investigated how aging modulates semantic encoding. We used a task where participants were required to determine the semantic relatedness between the cue and target stimuli. Single‐character Chinese words were the cues, whereas two‐character words describing the cues were the targets. The targets can be visual‐based (appearance) or associative‐based (meaning). Experiment One compared the reaction times on the two types of targets between older (n  = 29) and younger participants (n  = 31). Older participants performed significantly slower on the visual‐ than associative‐based trials, while the younger participants showed no difference. The results suggest that aging would hinder semantic encoding of visual‐ rather than associative‐based processes. The slowness in processing is likely attributable to age‐related decline in attentional control. Experiment Two tested the aging effect on top‐down attentional control by presenting pre‐cue before each trial on older (n  = 26) and younger participants (n  = 49). The results indicated that valid pre‐cue reduced the latency differences between the visual‐ and associative‐based trials among the older participants. The valid pre‐cues were found to effectively shorten the reaction time of the visual‐based trials suggesting possible facilitation of attentional control among the older adults. Our findings substantiate age‐related attentional control decline only in visual‐ but not associative‐based processing. Future studies should explore the mechanisms underlying such differential age‐related effect.     

Radical Copolymerization Behavior of 2,2‐Dimethyl‐5‐methylene‐1,3‐dioxolan‐4‐one with Common Monomers

Radical copolymerization of 2,2‐dimethyl‐1,3‐dioxolan‐4‐one (DMDO) consisting of a hybrid structure of acrylate and vinyl ether moieties with styrene, methyl methacrylate, and vinyl acetate was examined. The radical copolymerization was carried out without a solvent or in chlorobenzene in the presence of 3 mol‐% of 2,2′‐azoisobutyronitrile at 60°C for 20 h to obtain the copolymers with number‐average molecular weights of 1 400‐700 000 in 27–86% yields. No ring‐opening occurred but vinyl polymerization of DMDO selectively proceeded in the copolymerization. The monomer reactivity ratios were evaluated as r₁ = 6.42, r₂ = 0.08 (M₁, DMDO; M₂, styrene) by the Fineman‐Ross method. The Alfrey‐Price Q‐ and e‐values of DMDO were calculated as 5.97 and –0.13, respectively. Ab initio molecular orbital calculations were carried out to compare the reactivity of DMDO with methyl α‐methoxyacrylate and vinyl ether.     

Genetic association of interleukin‐2, interleukin‐4, interleukin‐6, transforming growth factor‐β, tumour necrosis factor‐α and blood concentrations of calcineurin inhibitors in Turkish renal transplant patients

Cytokines are essential for the control of the immune response as most of the immunosuppressive drugs target cytokine production or their action. The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are immunosuppressive drugs widely used after renal transplantation to prevent allograft rejection. They are characterized by large interindividual variability in their pharmacokinetics; therefore, monitoring their blood concentrations is important to predict their optimal dosage following transplantation. Calcineurin inhibitors inhibit the phosphatase activity of calcineurin, thereby suppressing the production of other cytokines such as transforming growth factor (TGF‐β), tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6, IL‐2, and IL‐4. The aim of this study was to investigate the relationship between polymorphisms of cytokines and blood concentrations of CNIs in renal transplant patients. The study included 53 CsA‐treated renal transplant patients and 37 tacrolimus‐treated renal transplant patients. Cytokine polymorphisms were analysed using polymerase chain reaction (PCR) sequence‐specific primers with the cytokine CTS‐PCR‐sequence‐specific primers Tray Kit; University of Heidelberg. Blood concentrations of CNIs were determined with Cloned Enzyme Donor Immunoassay (CEDIA) method. Patients with TC genotype of TGF‐β at codon 10 had lower CsA blood concentrations than the TT and CC genotypes (P = 0.005) at 1 month in CsA treatment group. The ratio of blood concentration/dose of CsA for patients with TGF‐β1‐codon 10 TC genotype was lower than for patients with TT, CC genotypes, and the dose given to these patients was higher in the first month (P = 0.046). The ratio of blood concentration/dose of CsA for patients with IL‐2‐330 GG genotype was higher than for patients with GT, TT genotypes, and the dose given to these patients was lower at first month and sixth months (P = 0.043, P = 0.035 respectively). The tacrolimus blood concentrations were significantly higher in patients with the genotype GG of IL‐2‐330 (P = 0.012) at the third month. Patients who had the TC genotype TGF‐β codon 10 had lower CsA blood concentrations and this group had higher acute rejection (P = 0.033). These results suggest that the genotyping for TGF‐β‐codon 10, IL‐2‐330 and IL‐6‐174 polymorphisms may help individualized immunosuppressive dosage regiments.     

Three‐dimensional ultrashort echo time cones T1ρ (3D UTE‐cones‐T1ρ) imaging

We report a novel three‐dimensional (3D) ultrashort echo time (UTE) sequence employing Cones trajectory and T_1ρ preparation (UTE‐Cones‐T_1ρ) for quantitative T_1ρ assessment of short T₂ tissues in the musculoskeletal system. A basic 3D UTE‐Cones sequence was combined with a spin‐locking preparation pulse for T_1ρ contrast. A relatively short TR was used to decrease the scan time, which required T₁ measurement and compensation using 3D UTE‐Cones data acquisitions with variable TRs. Another strategy to reduce the total scan time was to acquire multiple Cones spokes (N_sp) after each T_1ρ preparation and fat saturation. Four spin‐locking times (TSL = 0–20 ms) were acquired over 12 min, plus another 7 min for T₁ measurement. The 3D UTE‐Cones‐T_1ρ sequence was compared with a two‐dimensional (2D) spiral‐T_1ρ sequence for the imaging of a spherical CuSO₄ phantom and ex vivo meniscus and tendon specimens, as well as the knee and ankle joints of healthy volunteers, using a clinical 3‐T scanner. The CuSO₄ phantom showed a T_1ρ value of 76.5 ± 1.6 ms with the 2D spiral‐T_1ρ sequence, as well as 85.7 ± 3.6 and 89.2 ± 1.4 ms for the 3D UTE‐Cones‐T_1ρ sequences with N_sp of 1 and 5, respectively. The 3D UTE‐Cones‐T_1ρ sequence provided shorter T_1ρ values for the bovine meniscus sample relative to the 2D spiral‐T_1ρ sequence (10–12 ms versus 16 ms, respectively). The cadaveric human Achilles tendon sample could only be imaged with the 3D UTE‐Cones‐T_1ρ sequence (T_1ρ = 4.0 ± 0.9 ms), with the 2D spiral‐T_1ρ sequence demonstrating near‐zero signal intensity. Human studies yielded T_1ρ values of 36.1 ± 2.9, 18.3 ± 3.9 and 3.1 ± 0.4 ms for articular cartilage, meniscus and the Achilles tendon, respectively. The 3D UTE‐Cones‐T_1ρ sequence allows volumetric T_1ρ measurement of short T₂ tissues in vivo.     

Hybrid Hydrogel Networks by Photocrosslinking of Thermoresponsive α,ω‐Itaconyl‐PLGA‐PEG‐PLGA Micelles in Water: Influence of the Lithium Phenyl‐2,4,6‐Trimethylbenzoylphosphinate Photoinitinator

Modification of thermogelling biodegradable copolymers with functional groups enables further covalent crosslinking of physical micelle‐based hydrogels formed at specific temperature in water. The resulting hybrid hydrogel network exhibits an increase in stiffness and degradation stability. In this work, synthesized well‐defined thermoresponsive α,ω‐itaconyl‐poly(d ,l ‐lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactide‐co‐glycolide) (α,ω‐itaconyl‐PLGA‐PEG‐PLGA) macromonomers with a high degree of itaconyl‐substitution providing free double bonds are photocrosslinked in water at both 25 and 37 °C using lithium phenyl‐2,4,6‐trimethylbenzoylphosphinate (LiTPO) acting as water‐soluble non‐toxic photoinitiator. The effect of LiTPO on the thixotropic behavior of macromonomer in water at 25 °C without irradiation is evaluated. With the addition of a low amount of the photoinitiator (0.1 wt%), the degree of copolymer thixotropy increases. However, further increase in the photoinitiator concentration (0.5–3 wt%) leads to a lower degree of thixotropy. The photoinitiator is presumably interfering with the micellar self‐assembly of the copolymer. This trend is also reflected in photocrosslinking efficiency, where the hybrid hydrogel networks with the highest storage moduli are achieved with very low concentrations of the photoinitiator (0.1 wt%) at 25 °C, while this trend is reversed at 37 °C. The hydrolytic stability of hydrogels prepared at 37 °C from 17 wt% macromonomer solution with 1% LiTPO exceeds 22 days.     

Apnea‐related sleep fragmentation and poor vigilance in children with well‐controlled asthma

It has been reported that sleep problems and neurocognitive deficit in asthmatic children is prevalent. However, systematic studies on these problems in stable asthma using polysomnography have rarely been performed. We therefore investigated sleep and neurocognitive functioning in children with well‐controlled asthma. Forty‐three children with well‐controlled, stable asthma and 31 controls (age range: 6–9 years) were enrolled in the study. Subjects were questioned for daytime sleepiness using the Paediatric Daytime Sleepiness Scale. Complete overnight polysomnography and neurocognitive function tests were performed on all subjects. Children with stable asthma had lower pulmonary function in comparison to their age‐matched controls. Asthmatic children had a higher apnea–hypopnea index (P < 0.001) and apnea–hypopnea‐related arousal index (P < 0.001) as compared with non‐asthmatics. Deep sleep was decreased in asthmatics (P = 0.001). In the vigilance test, the mean number of correct answers was lower (P = 0.005) and the mean reaction time was slower (P = 0.002) in asthmatic children. A hierarchical multiple linear regression showed that deep sleep and apnea–hypopnea‐related arousal index were significant predictors of vigilance. The data suggest that the prevalence of paediatric sleep‐disordered breathing and sleep fragmentation could be very high among children with well‐controlled asthma. Moreover, vigilance, the ability to maintain attention and alertness, was worse in stable asthmatic children when compared with healthy controls. Sleep‐disordered breathing should be checked even in stable asthmatic children as they are at risk for developing neurobehavioural deterioration associated with frequent arousals during sleep. Furthermore, early treatment for asthma may be required in order to prevent airway remodelling that could cause sleep problems.     

Synthesis of a Polyphenol with a Mesoionic 6‐Oxo‐1,6‐dihydropyrimidin‐3‐ium‐4‐olate as Pendant Group and Its Photochemical Behavior

This study deals with the synthesis of a polyphenol bearing photosensitive groups, and its photochemical behavior upon UV irradiation. Mesoionic 5‐(4‐hydroxybenzyl)‐6‐oxo‐1,2,3‐triphenyl‐1,6‐dihydropyrimidin‐3‐ium‐4‐olate was prepared by condensation of 4‐benzyloxybenzylmalonic acid with N,N′‐diphenylbenzamidine using dicyclohexylcarbodiimide as condensing agent, followed by deprotection of the benzyl group. The monomer was polymerized by an iron‐salen complex to give a polymer with a mesoionic 6‐oxo‐1,6‐dihydropyrimidin‐3‐ium‐4‐olate moiety as the pendant group. Spin coated polymer films were prepared and characterized. It was shown by IR spectroscopy that irradiation with UV light converted the mesoionic structure to a bis(β‐lactam) structure. Waveguide spectroscopy showed a large decrease in the film thickness without refractive index changes during irradiation.

Time development of the refractive index and the film thickness measured with p‐polarized light.     

Role of medial prefrontal NMDA receptors in spatial delayed alternation in 19‐, 26‐, and 33‐day‐old rats

Long–Evans rats were trained on spatial delayed alteration (SDA) in a T‐maze following medial prefrontal cortical (mPFC) infusions of different doses of the noncompetitive NMDA‐receptor antagonist, MK‐801 (.125 µl; .25 µl; or .25 µlsaline, bilaterally), on postnatal day (PND) 19, 26, or 33. Pups trained on PND 19 showed almost no learning of SDA, regardless of drug condition (including saline). On PND 26, both doses of MK‐801 significantly and equivalently prevented SDA learning, with performance during the final three training blocks remaining near chance levels, in contrast with 85% correct performance in the saline control group. On PND 33, substantial SDA learning was evident regardless of dose, although a modest impairment appeared in mid‐training at both doses. These findings confirm previous reports of mPFC involvement in the early postnatal ontogeny of SDA and suggest a developmentally transient role of mPFC NMDA‐receptor function in this task. Dev. Psychobiol. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 583–591, 2010.     

Polymeric mesoions, 4. Synthesis of polymerizable mesoionic 4,6‐dioxo‐1,3‐diazines derived from vinylbenzylmalonic acid

Vinylbenzylmalonic acid ( 4 ) was condensed with N,N′‐diphenylformamidine ( 5 a ), N,N′‐diphenylacetamidine ( 5 b ), S‐propyl‐1,3‐diphenylisothiourea ( 6 ) and anilinopyridine ( 7 ) in the presence of dicyclohexylcarbodiimide (DCC). The resulting new mesoionic monomers 8 a – d were polymerized with 2,2′‐azoisobutyronitrile (AIBN) as an initiator and dodecanethiol as a chain transfer agent. The low molecular weight model compounds 5‐benzyl‐pyrido[1,2‐a]pyrimidine‐2,4‐dione ( 9 a ) and 5‐hexadecyl‐4,6‐dioxo‐1,3‐diphenyl‐2‐hexadecylthio‐1,3‐diazine ( 9 b ) were prepared for X‐ray diffraction analysis and comparison of spectroscopical data.     

Characteristics of Schistosoma japonicum infection induced IFN‐γ and IL‐4 co‐expressing plasticity Th cells

Schistosoma japonicum infection can induce granulomatous inflammation and cause tissue damage in the mouse liver. The cytokine secretion profile of T helper (Th) cells depends on both the nature of the activating stimulus and the local microenvironment (e.g. cytokines and other soluble factors). In the present study, we found an accumulation of large numbers of IFN‐γ⁺ IL‐4⁺ CD4⁺ T cells in mouse livers. This IFN‐γ⁺ IL‐4⁺ cell population increased from 0·68 ± 0·57% in uninfected mice to 7·05 ± 3·0% by week 4 following infection and to 9·6 ± 5·28% by week 6, before decreasing to 6·3 ± 5·9% by week 8 in CD4 T cells. Moreover, IFN‐γ⁺ IL‐4⁺ Th cells were also found in mouse spleen and mesenteric lymph nodes 6 weeks after infection. The majority of the IFN‐γ⁺ IL‐4⁺ Th cells were thought to be related to a state of immune activation, and some were memory T cells. Moreover, we found that these S. japonicum infection‐induced IFN‐γ⁺ IL‐4⁺ cells could express interleukin‐2 (IL‐2), IL‐9, IL‐17 and high IL‐10 levels at 6 weeks after S. japonicum infection. Taken together, our data suggest the existence of a population of IFN‐γ⁺ IL‐4⁺ plasticity effector/memory Th cells following S. japonicum infection in C57BL/6 mice.     

Study of the compatibility of poly[(styrene)‐co‐ (4‐vinylbenzoic acid)] with poly[(ethyl methacrylate)‐co‐(4‐vinylpyridine)] blends

Binary systems of poly[(ethyl methacrylate)‐co‐(4‐vinylpyridine)] (12.5 mol‐%), PEMAVP‐13, with poly[(styrene)‐co‐4‐(vinylbenzoic acid)] (3.5, 6.5 and 7.4 mol‐%), PSVBA, are investigated by differential scanning calorimetry and Fourier transform infrared spectroscopy. The calorimetric results show that PEMAVP‐13 is miscible with the three PSVBA copolymers in the studied proportions of 2 : 1, 1 : 1 and 1 : 2 by weight. The thermogram of each mixture shows a single composition‐dependent glass transition temperature, T_g. The experimental value of T_g for each blend is higher than the calculated weight average T_g of its components. Such a positive deviation implies the presence of strong specific interactions within these blends. A comparison of the determined Kwei q‐value reveals an increase of the specific interactions with acidic units in PSVBA composition. Fourier transform infrared measurements in the carbonyl stretching vibration region show the occurrence of hydrogen bonding involving the carboxylic acid groups of PSVBA with the carbonyl groups of PEMAVP‐13.     

Variation in human β‐defensin genes: new insights from a multi‐population study

Human β‐defensin 2 (hBD‐2) and hBD‐3, encoded by DEFB4 and DEFB103A, respectively, have shown anti‐HIV activity, and both genes exhibit copy number variation (CNV). Although the role of hBD‐1, encoded by DEFB1, in HIV‐1 infection is less clear, single nucleotide polymorphisms (SNPs) in DEFB1 may influence viral loads and disease progression. We examined the distribution of DEFB1 SNPs and DEFB4/103A CNV, and the relationship between DEFB1 SNPs and DEFB4/103A CNV using samples from two HIV/AIDS cohorts from the United States (n = 150) and five diverse populations from the Coriell Cell Repositories (n = 46). We determined the frequencies of 10 SNPs in DEFB1 using a post‐PCR, oligonucleotide ligation detection reaction–fluorescent microsphere assay, and CNV in DEFB4/103A by real‐time quantitative PCR. There were noticeable differences in the frequencies of DEFB1 SNP alleles and haplotypes among various racial/ethnic groups. The DEFB4/103A copy numbers varied from 2 to 8 (median, 4), and there was a significant difference between the copy numbers of self‐identified whites and blacks in the US cohorts (Mann–Whitney U‐test P = 0.04). A significant difference was observed in the distribution of DEFB4/103A CNV among DEFB1 ‐52G/A and ‐390T/A genotypes (Kruskal–Wallis P = 0.017 and 0.026, respectively), while not in the distribution of DEFB4/103A CNV among ‐52G/A_‐44C/G_‐20G/A diplotypes. These observations provide additional insights for further investigating the complex interplay between β‐defensin genetic polymorphisms and susceptibility to, or the progression or severity of, HIV infection/disease.     

Toddler's self‐regulation strategies in a challenge context are nap‐dependent

Early childhood represents a time of developmental changes in both sleep and self‐regulation, a construct reflecting the ability to control one's behaviour, attention and emotions when challenged. Links between sleep and self‐regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers’ self‐regulation. Healthy children (n = 12; four males; aged 30–36 months (33.9 ± 1.7)) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a nap and a no‐nap condition (~11‐day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self‐regulation strategies were later coded. On average, children lost ~90 min of sleep on the no‐nap versus the nap day. Nap deprivation resulted in moderate‐to‐large effects on self‐regulation strategies, with decreases in scepticism (d = 0.77; 7% change), negative self‐appraisal (d = 0.92; 5% change) and increases in physical self‐soothing (d = 0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d = 0.50; 9% change) and insistence on completing the unsolvable puzzle (d = 0.91; 10% change). Results suggest that sleep serves an important role in the way that toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to engage effectively in a difficult task and reverted to less mature self‐regulation strategies than when they were well rested. Over time, chronically missed sleep may impair young children's self‐regulation abilities, resulting in risk for social–emotional, behavioural and school problems.     

Synthesis of π‐Conjugated Organometallic Polymer Networks

The present paper reports the synthesis of π‐conjugated organometallic polymer networks based on poly[2,5‐dioctyloxy‐1,4‐diethynyl‐phenylene‐alt‐2,5,‐bis(2′‐ethylhexyloxy)‐1,4‐phenylene] (EHO‐OPPE), a soluble poly(p‐phenylene ethynylene) (PPE) derivative. The ethynylene moieties of the polymer coordinate to Pt⁰ centers, which act as conjugated cross‐links. These materials are readily accessible through ligand‐exchange reactions between the linear PPE and Pt(styrene)₃. The in‐situ NMR investigation of model reactions of Pt(styrene)₃ with diphenylacetylene (DPA) has shown that the ethynylene moieties comprised in the PPE readily coordinate to Pt⁰ centers under release of the relatively weakly‐bound styrene ligands. Spin‐coating has resulted in cross‐linked films of good optical quality. We also have been able to produce PPE‐Pt‐gels with high solvent content (> 95 wt.‐%). As expected, the coordination of Pt markedly influences the photophysical characteristics of the PPE. The photoluminescence is efficiently quenched, and the absorption maximum in the visible regime experiences a hypsochromic shift.

Ligand‐exchange reaction between EHO‐OPPE and [Pt(PhCH?CH₂)₃] leading to the target EHO‐OPPE‐Pt⁰ networks.     

Interferon‐γ enhances both the anti‐bacterial and the pro‐inflammatory response of human mast cells to Staphylococcus aureus

Human mast cells (huMCs) are involved in both innate and adaptive immune responses where they release mediators including amines, reactive oxygen species (ROS), eicosanoids and cytokines. We have reported that interferon‐γ (IFN‐γ) enhances FcγR‐dependent ROS production. The aim of this study was to extend these observations by investigating the effect of IFN‐γ on the biological responses of huMCs to Staphylococcus aureus. We found that exposure of huMCs to S. aureus generated intracellular and extracellular ROS, which were enhanced in the presence of IFN‐γ. IFN‐γ also promoted bacteria killing, β‐hexosaminidase release and eicosanoid production. Interferon‐γ similarly increased expression of mRNAs encoding CCL1 to CCL4, granulocyte–macrophage colony‐stimulating factor (GM‐CSF), tumour necrosis factor‐α and CXCL8 in S. aureus‐stimulated huMCs. The ability of IFN‐γ to increase CXCL8 and GM‐CSF protein levels was confirmed by ELISA. Fibronectin or a β₁ integrin blocking antibody completely abrogated IFN‐γ‐dependent S. aureus binding and reduced S. aureus‐dependent CXCL8 secretion. These data demonstrate that IFN‐γ primes huMCs for enhanced anti‐bacterial and pro‐inflammatory responses to S. aureus, partially mediated by β₁ integrin.