Thyroid hormone dynamics of Tharparkar and Sahiwal cattle during induced heat stress.

Thyroid hormones and Cortisol level are the essential biomarkers in the assessment of stress condition. This study was done to estimate the metabolic hormonal profile of Tharparkar and Sahiwal during heat stress condition. The experiment was conducted on two groups consisting of Tharparkar and Sahiwal animals (5 in each group) and the experimental period comprised a 7-day acclimatization period, a heat exposure period of 21 days at control (25 °C), moderate (35 °C) and severe (42 °C) heat stress within a 9-10-day recovery period between each exposure. The hormonal concentrations of T3, T4 and cortisol were determined in serum. The serum concentration of Thyroxine (T4) and tri-iodothyronine (T3) decreases whereas cortisol level increases in both the breeds when subjected to heat stress. However, the serum level of T4 was significantly (p < 0.05) more declined in Sahiwal as compared to Tharparkar but there was no significant difference found between the two breeds in serum T3 levels. The cortisol levels were elevated in both breeds during heat stress but significantly (p < 0.05) more elevated in the Sahiwal. Hence, observations of these hormonal profiles suggest a better thermo-adaptability in Tharparkar as compared to Sahiwal.

Modification of the Fitzpatrick system of skin phototype classification for the Indian population, and its correlation with narrowband diffuse reflectance spectrophotometry.

BACKGROUND: The Fitzpatrick classification for skin phototyping is widely used, but its usefulness in dark-skinned populations has been questioned by some researchers. Recently, skin colour measurement has been proposed for phototyping skin colour objectively. AIMS: To modify the Fitzpatrick system of skin phototyping for the Indian population and to study its correlation with skin colour using narrowband diffuse reflectance spectrophotometry METHODS: Answer choices for three items (eye colour, hair colour, colour of unexposed skin) out of 10 in the original Fitzpatrick questionnaire were modified, followed by self-administration of the original and the modified Fitzpatrick questionnaire by 70 healthy Indian volunteers. Skin colour (melanin and erythema indices) was measured from two photoexposed and two photoprotected sites using a narrowband reflectance spectrophotometer. RESULTS: The mean ± SD scores for the original and modified Fitzpatrick questionnaires were 25.40 ± 4.49 and 23.89 ± 4.82, respectively (r = 0.97, P < 0.001). The two items related to tanning habits were deemed irrelevant based on the subjects' response and were removed from the modified questionnaire. The Melanin Index (MI) of all sites correlated moderately well with both the modified (r = 0.61-0.64, P < 0.001) and original Fitzpatrick questionnaire scores (r = 0.64-0.67, P < 0.001), while the Erythema Index showed poor correlation with both. An MI value of ≧42 was found to be the cut-off between skin phototypes I-III and IV, and ≥ 47 between IV and V-VI. CONCLUSIONS: Our modification of the Fitzpatrick questionnaire makes it more relevant to the Indian population. Spectrophotometry can be a useful objective tool for skin phototyping.

Association of the Apolipoprotein A-I Gene Polymorphisms with Cardiovascular Disease Risk Factors and Atherogenic Indices in Patients from Assam, Northeast India.

Cardiovascular disease (CVD) risk factors, and particularly decreased high density lipoprotein cholesterol (HDL-C) dyslipidemia are prevalent in Assam, India. This study was undertaken to investigate whether Apolipoprotein A-I (APOA1) gene polymorphisms (G-75A and C+83T) were associated with i) the risk for decreased HDL-C, and ii) other CVD risk factors, viz. serum lipids, atherogenic indices, obesity, and blood pressure (BP). A total of 649 subjects were screened, from which 200 eligible individuals, classified as case group with decreased HDL-C levels (100 subjects) and control group with normal HDL-C levels (100 subjects) were enrolled and genotyped using polymersase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Lipid fractions [HDL-C, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG)] and atherogenic indices [Castelli's Risk Indices-I and -II (CRI-I and -II), non-HDL-C fraction, atherogenic index of plasma (AIP), atherogenic coefficient (AC)] were estimated. The G-75A and C+83T loci were not associated with decreased HDL-C risk. This was confirmed across different genetic models (dominant, recessive, additive and allelic). Association was also absent with BP and obesity. However, the G-75A locus was associated with LDL-C, whereas the C+83T locus was associated with TG and VLDL-C. Furthermore, these sites had effects on atherogenic indices. The rare A allele at the G-75A locus was associated with adverse CRI-I, CRI-II, non-HDL-C and AC values, while the major C allele at the C+83T locus was associated with adverse AIP values. Thus, the pro-atherogenic G-75A polymorphism and the anti-atherogenic C+83T polymorphism represent important genetic loci that modulate CVD risk factors in subjects from Assam.

Membrane biophysics define neuron and astrocyte progenitors in the neural lineage.

Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. Accurately identifying and characterizing the different progenitor cells in this lineage has continued to be a challenge for the field. We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). Here, we hypothesize that inherent electrophysiological properties are sufficient to define NPs and APs and test this by determining whether isolation of cells solely by these properties specifically separates NPs and APs. We found NPs and APs are enriched in distinct fractions after separation by electrophysiological properties using DEP. A single round of DEP isolation provided greater NP enrichment than sorting with PSA-NCAM, which is considered an NP marker. Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface.

Uterine infection influences size and follicular fluid composition of the largest follicle in buffalo (Bubalus bubalis).

The effect of uterine infection on size and follicular fluid composition of the largest follicle was studied in buffalo. Reproductive tracts were collected from 102 graded Murrah buffaloes at an abattoir. Uterine infection was diagnosed by physical examination of uterine mucus, white side test and uterine cytology. Samples with pus-containing mucus, positive reaction on white side test and/or >5% neutrophils were considered to be positive for uterine infection. Diameter of the largest follicle was measured, and follicular fluid was aspirated and assayed for nitric oxide (NO), ascorbic acid (AA), cholesterol, oestradiol (E(2)) and progesterone (P(4)). Infected buffaloes had smaller-sized (p < 0.0001) largest follicles than non-infected buffaloes. Follicular fluid collected from the largest follicle in infected buffaloes had greater (p < 0.0001) NO and P(4) concentrations coincident with lesser AA (p < 0.001), cholesterol (p < 0.0001) and E(2) (p < 0.0001) concentrations. Results indicated that uterine infection has an inhibitory effect on growth of the largest follicle in buffalo. The changes in follicular fluid composition in infected buffaloes suggest that the direct effect of uterine infection on ovarian function may be mediated through an alteration in the follicular microenvironment. Greater NO and lesser AA concentrations in the follicular fluid of infected animals are novel findings.

Particulate matter concentration in ambient air and its effects on lung functions among residents in the National Capital Region, India.

The World Health Organization has estimated that air pollution is responsible for 1.4 % of all deaths and 0.8 % of disability-adjusted life years. NOIDA, located at the National Capital Region, India, was declared as one of the critically air-polluted areas by the Central Pollution Control Board of the Government of India. Studies on the relationship of reduction in lung functions of residents living in areas with higher concentrations of particulate matter (PM) in ambient air were inconclusive since the subjects of most of the studies are hospital admission cases. Very few studies, including one from India, have shown the relationship of PM concentration and its effects of lung functions in the same location. Hence, a cross-sectional study was undertaken to study the effect of particulate matter concentration in ambient air on the lung functions of residents living in a critically air-polluted area in India. PM concentrations in ambient air (PM(1,) PM(2.5)) were monitored at residential locations and identified locations with higher (NOIDA) and lower concentrations (Gurgaon). Lung function tests (FEV(1), PEFR) were conducted using a spirometer in 757 residents. Both air monitoring and lung function tests were conducted on the same day. Significant negative linear relationship exists between higher concentrations of PM(1) with reduced FEV(1) and increased concentrations of PM(2.5) with reduced PEFR and FEV(1). The study shows that reductions in lung functions (PEFR and FEV(1)) can be attributed to higher particulate matter concentrations in ambient air. Decline in airflow obstruction in subjects exposed to high PM concentrations can be attributed to the fibrogenic response and associated airway wall remodeling. The study suggests the intervention of policy makers and stake holders to take necessary steps to reduce the emissions of PM concentrations, especially PM(1,) PM(2.5), which can lead to serious respiratory health concerns in residents.

Spatial heterogeneity in global atmospheric CO during the COVID-19 lockdown: Implications for global and regional air quality policies.

The COVID-19 lockdown (LD) provided a unique opportunity to examine the changes in regional and global air quality. Changes in the atmospheric carbon monoxide (CO) during LD warrant a thorough analysis as CO is a major air pollutant that affects human health, ecosystem and climate. Our analysis reveals a decrease of 5-10% in the CO column during LD (April-May 2020) compared to the pre-lockdown (PreLD, March 2020) periods in regions with high anthropogenic activity, such as East China (EC), Indo-Gangetic Plain (IGP), North America, parts of Europe and Russia. However, this reduction did not occur in the regions of frequent and intense wildfires and agricultural waste burning (AWB). We find high heterogeneity in the CO column distributions, from regional to city scales during the LD period. To determine the sources of CO emissions during LD, we examined the ratios of nitrogen dioxide (NO2), sulfur dioxide (SO2) to CO for major cities in the world. This facilitated the identification of contributions from different sources; including vehicles, industries and biomass burning during LD. The comparison between CO levels during the LD and PreLD periods indicates a notable reduction in the global tropospheric CO, but no significant change in the stratosphere. It is found that CO emissions decreased during LD in the hotspot regions, but rebounded after the LD restrictions were lifted. This study, therefore, highlights the importance of policy decisions and their implementations in the global and regional scales to improve the air quality, and thus to protect public health and environment.

Adoption of cleaner technologies and reduction in fire events in the hotspots lead to global decline in carbon monoxide.

Carbon Monoxide (CO) is not a greenhouse gas (GHG), but has the capacity to change atmospheric chemistry of other GHGs such as methane and ozone, and therefore indirectly affects Earth's radiative forcing of the GHGs and surface temperature. Here, we use the CO mixing ratio at 850 hPa from the Tropospheric Emission Spectrometer (TES) reanalysis and the Measurement of Pollution in the Troposphere (MOPITT) satellite measurements for the period 2005-2019 to examine the spatio-temporal changes in CO across the latitudes. We find a substantial decrease in global CO, about -0.21 ± 0.09 ppb/yr (-0.23 ± 0.12%/yr) with the TES data and about -0.36 ± 0.07 ppb/yr (-0.45 ± 0.08%/yr) with the MOPITT satellite measurements during the study period. The highest CO decreasing trend is observed in Eastern China (-2.7 ± 0.37 ppb/yr) followed by Myanmar (-2.142 ± 0.59 ppb/yr) and South America (-1.08 ± 0.82 ppb/yr). This negative trend in CO is primarily due to the decrease in biomass burning and stringent environmental regulations in the respective regions and countries. The sources including road transport, which account for about 33.6% of CO emissions, followed by industries (18.3%) and agricultural waste burning (8.8%), might also be responsible for the reduction in CO due to the adaptation of improved emission control technology and regulations in the past decades from 2005 to 2019. Therefore, the study provides new insights on the current trends of global CO distribution and reasons for recent reduction in global CO emissions, which would be useful for future decision-making process to control air pollution.

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice.

INTRODUCTION: Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals. RESULTS: Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots. CONCLUSIONS: We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.

Establishment of effective and safe recipient preparation for germ-cell transplantation with intra-testicular busulfan treatment in pre-pubertal Barbari goats.

The busulfan, an alkylating agent, suppresses endogenous spermatogenesis in recipient testes. However, considering a wide variation in the effects of busulfan among animal species, its dosage and route of infusion need optimization to prepare effective and safe recipients. Thus, the current study aimed to create a suitable recipient goat model for germ cell (Gc) transplantation through a single intra-testicular (i.t.) busulfan infusion under ultrasonographic (USG) guidance. As observed through the infusion of trypan blue under USG guidance into mediastinum testis (MT) of pre-pubertal Barbari bucks, 3-5 mL of trypan blue solution could fill almost 80% of seminiferous tubules. Thereafter, in Experiment-1, the effect of different busulfan doses (mg/kg) i.e. 0 [negative control, Group (Gr) 1; 0 mg/kg-MT], 1 (Gr 2; 1 mg/kg-MT), 2 (Gr 3; 2 mg/kg-MT), and 3 (Gr 4; 3 mg/kg-MT) were studied. Further, in Experiment-2, sterilizing effects of busulfan infusion through two different routes [MT or cavum vaginale (CV)] were compared. Following i.t. busulfan treatment, no adverse physiological effects or body weight loss were detected. The histological analyses demonstrate a dose-dependent depletion of Gc with almost complete loss of Gc and spermatogenic activities in Gr 3 and 4, and extensive fibrosis in Gr 4. A considerable suppression of spermatogenesis marked with devoid of endogenous spermatogonial population and absence of significant (P > 0.05) effect on key hematological variables were observed in 2 mg/kg-MT Gr. These findings coupled with the results of significant (P < 0.05) down-regulation of marker genes of undifferentiated spermatogonia (THY-1 and PLZF), Gc pluripotency (UCHL-1, OCT-4, and DDX-4), and adhesion (E-cadherin and ß-integrin); up-regulation of apoptotic genes (ID - 4 and BCL-6), and unchanged expression of Sertoli cell marker (vimentin), confirmed the safe and efficient depletion of endogenous Gc in 2 mg/kg-MT Gr. Furthermore, the effect of busulfan infusion on scrotal-testicular biometry, endocrine variables (plasma cortisol and testosterone), and Gc removal was more evident when busulfan was infused into MT than into CV. Overall, the results demonstrated that 2.0 mg/kg is an optimal single dose of busulfan when infused into the MT under USG guidance for the preparation of pre-pubertal recipient bucks. Overall, this study provides a basis to prepare suitable recipients through providing an available niche for efficient Gc transplantation in goats.

Cholinesterase levels and morbidity in pesticide sprayers in North India.

BACKGROUND: Pesticide sprayers in North India use different application methods for different crops. AIMS: To compare cholinesterase activity and symptoms in knapsack and tractor-mounted pesticide sprayers. METHODS: Blood cholinesterase activity and symptoms were recorded for 42 knapsack and 66 tractor-mounted sprayers attending a health camp in North India in 2009 and for 30 controls. RESULTS: One hundred and eight of 197 (55%) eligible sprayers consented to participate. Mean acetylcholinesterase (AChE) and butyrylcholinesterase activity was 33 and 60% lower, respectively, in knapsack sprayers than in controls (P < 0.001) and 56 and 62% lower, respectively, in tractor-mounted sprayers than in controls (P < 0.001). AChE depletion was greater in tractor-mounted sprayers than in knapsack sprayers (P < 0.001). In knapsack sprayers compared to controls, odds ratios (OR) were significantly raised for musculoskeletal symptoms (OR 3.9, 95% CI 1.03-18) but not for other symptoms. In tractor-mounted sprayers compared to controls, ORs were significantly raised for neurological (OR 7, 95% CI 2-23), ocular (OR 8.7, 95% CI 2.7-32), respiratory (OR 5.14, 95% CI 1-29), cardiovascular (OR 7.5, 95% CI 2-42), gastrointestinal (OR 5.43, 95% CI 2-18) and musculoskeletal (OR 6.12, 95% CI 2-26) symptoms but not for dermal symptoms (OR 1.93, 95% CI 0.3-20). CONCLUSIONS: The risk of cholinesterase inhibition and symptoms is greater in tractor-mounted than in knapsack pesticide sprayers and in both groups compared to controls. Occupational exposure in pesticide sprayers in North India needs better control, perhaps through redesign of spraying equipment.

Thrombin in the Activation of the Fluid Contact Phase in Patients with Hereditary Angioedema Carrying the F12 P.Thr309Lys Variant.

Hereditary angioedema due to pathogenic FXII variants (HAE-FXII) is a rare dominant disease caused by increased activation of the plasma contact system. The most prevalent HAE-FXII variant, c.1032C > A p.Thr309Lys (FXII309Lys), results in a smaller FXII protein with increased sensitivity to fluid-phase activation by poorly understood mechanisms. We aimed to investigate the functionality of the FXII309Lys variant in 33 HAE-FXII patients, 25 healthy controls and 46 patients with congenital disorders of glycosylation (CDG). Activation of the plasma contact system was assessed by western blot and amidolytic assay in basal conditions or after treatment with either artificial or physiological activators. Recombinant wild-type and FXII309Lys variants were expressed in S2 insect (Drosophila) cells. Amidolytic and fibrin generation assays were performed in fresh plasma samples. FXII309Lys samples exhibited an increased electrophoretic mobility comparable with N-glycan-deficient FXII from CDG patients and asialo-FXII generated by neuraminidase treatment. They presented increased sensitivity to activation by dextran sulphate and silica which resulted in the generation of an aberrant 37-kDa heavy chain. We did not observe increased susceptibility of FXII309Lys to proteolysis by exogenous or tPA-generated plasmin. However, both exogenous and endogenous thrombin cleaved the FXII309Lys variant, releasing a 37-kDa fragment and resulting in enhanced proteolytic activation on the fluid phase. This model supports a sequential proteolytic activation process involving thrombin priming of FXII309Lys, followed by kallikrein cleavage and generation of active ßFXIIa. The present results and the observation that angioedema episodes in HAE-FXII patients occur predominantly during hypercoagulable situations suggest a key role for thrombin.

Photochemotherapy: identification of a metabolite of 4, 5', 8-trimethylpsoralen.

A compound, 4, 8-dimethyl, 5'-carboxypsoralen (DMeCP), has been identified in mouse urine as a major metabolite of the photoactive drug, 4, 5', 8-trimethylpsoralen (TMeP). This drug is widely used in the treatment of vitiligo and psoriasis. DMeCP is fluorescent, and nonphotosensitizing when tested on guinea pig skin. DMeCP also occurs in the urine of human patients receiving TMeP orally.

Sm3+ doped calcium orthovanadate Ca3(VO4)2 - A spectral study.

Sm3+-doped vanadate-based phosphors, Ca3-x (VO4)2:Smx(x = 0.005 ≤ x ≤ 0.095), were synthesized by the citrate-based sol-gel method. The samples were characterized with XRD, SEM, diffuse reflectance and photoluminescence spectroscopy, aiming at the development of phosphor-converted wLED applications. Using diffuse reflectance spectra and the Kubelka-Munk function, the band gap energy was calculated to be 3.28 eV for the Ca2.95(VO4)2:Sm0.05 phosphor. Observation of the photoluminescence excitation spectra revealed a broadband excitation from the distorted VO4 tetrahedron and a few narrow peaks from the 4f-4f intra-configuration transitions of the Sm3+ ions. Upon 404 nm excitation, 4G5/2 → 6H5/2 (564 nm), 4G5/2 → 6H7/2 (601 nm), 4G5/2 → 6H9/2 (648 nm) and 4G5/2 → 6H11/2 (701 nm) transitions were observed. The optimum Sm3+ concentration for the studied phosphor is 0.05 mol, and the estimated critical distance between Sm3+ ions (Rc) is 19.1 Å. The observed quenching of Sm3+ emission is attributed to the dipole-dipole interactions. The possible cross-relaxation process between neighboring Sm3+ ions was discussed in detail. The CIE coordinates were calculated for all the samples, and they set on the orange region of CIE diagram. In addition, pure orange color emission was observed under 365 nm UV lamp. The results suggest that the Ca3(VO4)2:Sm3+ phosphor could be a good candidate for the orange emitting component for wLED applications.

Erythropoietic protoporphyria. Photoactivation of the complement system.

The complement system was analysed in 14 asymptomatic patients with erythropoietic protoporphyria. In the majority of the sera studied the levels of complement components C1, C4, C2, and C3 were within the normal range. Upon ultraviolet light (330--460 nm) irradiation of the serum samples in vitro, a marked decrease in total hemolytic activity accompanied by reduction of C1, C4, C2, and C3 levels was observed. The loss of total hemolytic activity can be directly correlated with the levels of protoporphyrin (PP) and similar changes can be obtained in normal serum upon addition of PP followedf by ultraviolet light irradiation. It is postulated that after irradiation the excited PP develops the capacity to activate the complement sequence with the production of cleavage products, which may contribute to the skin changes observed in these patients upon sun exposure.

Dietary lutein/zeaxanthin partially reduces photoaging and photocarcinogenesis in chronically UVB-irradiated Skh-1 hairless mice.

Lutein and zeaxanthin are xanthophyll carotenoids with potent antioxidant properties protecting the skin from acute photodamage. This study extended the investigation to chronic photodamage and photocarcinogenesis. Mice received either a lutein/zeaxanthin-supplemented diet or a standard nonsupplemented diet. Dorsal skin of female Skh-1 hairless mice was exposed to UVB radiation with a cumulative dose of 16,000 mJ/cm(2) for photoaging and 30,200 mJ/cm(2) for photocarcinogenesis. Clinical evaluations were performed weekly, and the animals were sacrificed 24 h after the last UVB exposure. For photoaging experiments, skin fold thickness, suprapapillary plate thickness, mast cell counts and dermal desmosine content were evaluated. For photocarcinogenesis, samples of tumors larger than 2 mm were analyzed for histological characterization, hyperproliferation index, tumor multiplicity, total tumor volume and tumor-free survival time. Results of the photoaging experiment revealed that skin fold thickness and number of infiltrating mast cells following UVB irradiation were significantly less in lutein/zeaxanthin-treated mice when compared to irradiated animals fed the standard diet. The results of the photocarcinogenesis experiment were increased tumor-free survival time, reduced tumor multiplicity and total tumor volume in lutein/zeaxanthin-treated mice in comparison with control irradiated animals fed the standard diet. These data demonstrate that dietary lutein/zeaxanthin supplementation protects the skin against UVB-induced photoaging and photocarcinogenesis.

Assessment of the protein interaction between coagulation factor XII and corn trypsin inhibitor by molecular docking and biochemical validation.

Essentials Corn Trypsin Inhibitor (CTI) is a selective inhibitor of coagulation Factor XII (FXII). Molecular modelling of the CTI-FXIIa complex suggested a canonical inhibitor binding mode. Mutagenesis revealed the CTI inhibitory loop and helices α1 and α2 mediate the interaction. This confirms that CTI inhibits FXII in canonical fashion and validates the molecular model. SUMMARY: Background Corn trypsin inhibitor (CTI) has selectivity for the serine proteases coagulation factor XII and trypsin. CTI is in widespread use as a reagent that specifically inhibits the intrinsic pathway of blood coagulation but not the extrinsic pathway. Objectives To investigate the molecular basis of FXII inhibition by CTI. Methods We performed molecular docking of CTI, using its known crystal structure, with a model of the activated FXII (FXIIa) protease domain. The interaction model was verified by use of a panel of recombinant CTI variants tested for their ability to inhibit FXIIa enzymatic activity in a substrate cleavage assay. Results The docking predicted that: (i) the CTI central inhibitory loop P1 Arg34 side chain forms a salt bridge with the FXIIa S1 pocket Asp189 side chain; (ii) Trp22 from CTI helix α1 interacts with the FXIIa S3 pocket; and (iii) Arg43 from CTI helix α2 forms a salt bridge with FXIIa H1 pocket Asp60A. CTI amino acid substitution R34A negated all inhibitory activity, whereas the G32W, L35A, W22A and R42A/R43A substitutions reduced activity by large degrees of 108-fold, 41-fold, 158-fold, and 100-fold, respectively; the R27A, W37A, W39A and R42A substitutions had no effect. Synthetic peptides spanning CTI residues 20-44 had inhibitory activity that was three-fold to 4000-fold less than that of full-length CTI. Conclusions The data confirm the validity of a canonical model of the FXIIa-CTI interaction, with helix α1 (Trp22), central inhibitory loop (Arg34) and helix α2 (Arg43) of CTI being required for effective binding by contacting the S1, S3 and H1 pockets of FXIIa, respectively.

Visible upconversion in Er3+/Yb3+ co-doped LaAlO3 phosphors.

The Er3+ doped and Er3+/Yb3+ co-doped LaAlO3 phosphors have been synthesized by the combustion method and characterized their structural, morphological, elemental, vibrational and optical properties. The optical absorption and upconversion properties of the synthesized phosphors have been studied. Upon co-doping Yb3+ ions into Er3+:LaAlO3, the blue, green and red upconversion emissions of Er3+ ions have been enhanced about ~20, ~54 and ~22 times, under 978nm laser excitation. The observed upconversion emissions could be due to excited state absorption in Er3+:LaAlO3, whereas energy transfer is dominant mechanism in Er3+/Yb3+:LaAlO3 phosphors. The tuning in the color emitted from the synthesized phosphors towards the green region has been found due to incorporation of the Yb3+ ions. With increase in the pump power, the color emitted from the co-doped phosphor is not tuned significantly, showing its applicability in making the green display devices.

Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease.

Type 1 interferon (IFN-1) promotes regulatory T-cell function to suppress inflammation in the mouse intestine, but little is known about IFN-1 in the human gut. We therefore assessed the influence of IFN-1 on CD4+ T-cells isolated from human colon tissue obtained from healthy controls or patients with inflammatory bowel disease (IBD). Immunofluorescent imaging revealed constitutive expression of IFNß in human intestinal tissue, and colonic T-cells were responsive to exogenous IFN-1 as assessed by phosphorylation of signal transduction and activator of transcription 1 (pSTAT1) and induction of interferon stimulated genes (ISGs). Unlike their blood counterparts, intestinal T-cells from non-inflamed regions of IBD colon displayed enhanced responsiveness to IFN-1, increased frequency of pSTAT1+ cells, and greater induction of ISGs upon IFN-1 exposure in vitro. In healthy tissue, antibody neutralization of IFNß selectively reduced T-cell production of the pro-regulatory cytokine interleukin-10 (IL-10) and increased IFNγ synthesis. In contrast, neutralization of IFNß in IBD tissue cultures increased the frequency of T-cells producing inflammatory cytokines but did not alter IL-10 expression. These data support a role for endogenous IFN-1 as a context-dependent modulator of T-cell function that promotes regulatory activity in healthy human intestine, but indicate that the IFN-1/STAT1 pathway is dysregulated in inflammatory bowel disease.

Molecular aspects of drug photosensitivity with special emphasis on psoralen photosensitization reaction.

Photosensitization reactions involve phototoxic reactions and photoallergic reactions, which are less common. Common drugs and chemicals that photosensitize humans are listed. Phototoxic reactions include the following: 1) direct photosensitization (type I reactions), in which the reactions of the triplet-state sensitizer are directly attributable to a component other than oxygen (e.g., DNA, proteins, and cell membranes), and 2) indirect photosensitization (type II reactions), in which the triplet state of a sensitizer reacts first with molecular oxygen, producing an "active oxygen" intermediate that subsequently reacts with the biologic system. The active oxygen intermediates are singlet oxygen (1O2)k, superoxide radical anions (O(2), and hydroxy radicals. Psoralen-induced skin photosensitization appears to involve both type I and type II reactions. The formation of monofunctional bifunctional psoralen-DNA photoadducts (a type I reaction) is probably responsible for cell damage, cell death, mutation, and even skin carcinogenesis. The erythema response appears to be the result of a type II reaction.