Seroprevalence of infectious laryngotracheitis disease in backyard chickens in villages of Ada'a district, Oromia, Ethiopia: first report.

As per the report from the OIE in 2005, infectious laryngotracheitis (ILT) has not been yet reported in Ethiopia. Hence, considering the evident clinical signs on-field associated with the disease, it felt that there is a need to identify the disease and to protect the chicken population. The study was, therefore, aimed at identifying the seroprevalence of ILT virus from the samples collected from chickens in backyard system, so as to notify its prevalence and setup recommendations for further research in the future. Consequently, cross-sectional study was conducted in eleven purposefully selected peasant associations (PA) of Ada'a district from January to May 2019 to determine ILT in backyard chickens. A total number of 426 sera sample of backyard chickens were randomly collected from 11 PA and each sera was exposed to an indirect enzyme-linked immunosorbent assay (iELISA), at the National Animal Health Diagnostic and Investigation Center, Ethiopia. Out of 426 samples, 233 (54.7%) samples were found positive for ILT virus-specific antibody. The highest prevalence was recorded in Wajitu (83.3%), whereas the least was in Giche (40.7%) PA. There was a statistically significant difference (p < 0.05) among seroprevalence and study PA. The result of this study revealed that a high prevalence of ILT virus is circulating among backyard chickens in the selected PA of Ada'a district, which could significantly affect the poultry sector. Thus, further studies on the circulating strains and the epidemiology of the disease should be carried using a molecular diagnostic test.

Seasonal variation of strongylosis in working donkeys of Ethiopia: a cross-sectional and longitudinal studies.

Helminths are one of the major health problems of working donkeys, often with heavy worm burden and contributing to their early demise and/or reduction in their work output. Cross-sectional and longitudinal studies were conducted to investigate the current infection prevalence and level of strongyles infection donkeys would acquire through different seasons in the mid-lowland agro-ecological zones of Ethiopia. For this purpose, faecal samples from 206 (cross-sectional study) and 102 (longitudinal study) randomly selected donkeys were directly collected from the rectum and analysed. For the longitudinal study, the 102 donkeys dewormed at the end of main rainy season, beginning of October, were monitored for the level of strongyle infection they would acquire during subsequent dry and short rainy seasons. The cross-sectional study of 206 donkey has revealed an overall infection prevalence of 89.3% (95% confidence interval (CI) = 84.4, 92.9). Donkeys in the lowland zone showed a significantly higher strongyle infection prevalence (P = 0.0126) and mean eggs per gramme of faces (EPG) (P = 0.001; 2775 EPG) compared to donkeys in the midland zone (980.8 EPG). Age, sex and body condition did not have any significant effect on either the infection prevalence or level of infection (P > 0.05). The longitudinal study has shown a significantly lower strongyle infection prevalence (P = 0.003) and level of infection donkeys acquired (P = 0.001) in the subsequent dry and short rainy seasons compared to the main rainy season following October deworming. However, these values were not significantly different between the two agro-ecological zones (P > 0.05). This study clearly showed that parasitic infections are primarily acquired during the main rainy season when pasture/herbage coverage is relatively better, and the environment is conducive for parasites survival and development. On the other hand, the finding of majority of donkeys shedding low or no eggs during the dry and short rainy seasons showed that October deworming was effective, and donkeys acquire low or no parasitic infection during the subsequent dry and short rainy seasons. Therefore, the practice of anthelmintic treatment of donkeys at the end of short rain in May may not be necessary, and October deworming once a year is sufficient.

Equine colic: clinical epidemiology and associated risk factors in and around Debre Zeit.

A prospective study was conducted to describe clinical epidemiology of equine colic in the Society for Protection of Animal Abroad and Donkey Sanctuary Project Clinic, at Debre Zeit, Ethiopia, from November 2014 to April 2015. The objectives were to describe clinical epidemiology of equine colic, to characterize the main types of equine colic, and to determine the major risk factors associated with equine colic. The method which was used in the study was attending clinical case of equine and assessing physiological parameters, fecal egg count, abdominal sounds, and rectal examination as well as questioner interviewing of the owners. The data were collected and analyzed using Statistical Package for Social Science. The incidence of colic was 10.3% in the study period. Colicky were typed as unknown, flatulent, impaction, spasmodic, and enterolithiasis. The proportion of case incidence were 63.1 (41/65), 33.8 (22/65), and 3.1% (2/65), in donkey, horse, and mule, respectively. The total mean (±SD) of temperature 37.80 ± 1.003, heart rate 57.54 ± 10.098, fecal egg count 236.922 ± 67.990, respiratory rate 30.92 ± 7.315, and packed cell volume 41.40 ± 10.221 were recorded. The case fatality rate of equine colic was 15.38% (10/65). There were statistically highly significant (p < 0.01) differences in impaction colic in relation to species. Interview with 183 equine owners revealed incidence of equine colic as the sixth major disease condition affecting equine. A long-term epidemiological study of the true representative population should be carried out to determine the incidence rate and associated risk factors of equine colic in the study area.

Direct effect of glucocorticoids on glucose-activated adult rat ß-cells increases their cell number and their functional mass for transplantation.

Compounds that increase ß-cell number can serve as ß-cell replacement therapies in diabetes. In vitro studies have identified several agents that can activate DNA synthesis in primary ß-cells but only in small percentages of cells and without demonstration of increases in cell number. We used whole well multiparameter imaging to first screen a library of 1,280 compounds for their ability to recruit adult rat ß-cells into DNA synthesis and then assessed influences of stimulatory agents on the number of living cells. The four compounds with highest ß-cell recruitment were glucocorticoid (GC) receptor ligands. The GC effect occurred in glucose-activated ß-cells and was associated with increased glucose utilization and oxidation. Hydrocortisone and methylprednisolone almost doubled the number of ß-cells in 2 wk. The expanded cell population provided an increased functional ß-cell mass for transplantation in diabetic animals. These effects are age dependent; they did not occur in neonatal rat ß-cells, where GC exposure suppressed basal replication and was cytotoxic. We concluded that GCs can induce the replication of adult rat ß-cells through a direct action, with intercellular differences in responsiveness that have been related to differences in glucose activation and in age. These influences can explain variability in GC-induced activation of DNA synthesis in rat and human ß-cells. Our study also demonstrated that ß-cells can be expanded in vitro to increase the size of metabolically adequate grafts.

(E)-3-(4-Heptyl-oxyphen-yl)-1-phenyl-prop-2-en-1-one.

In the title compound, C22H26O2, the aromatic rings are inclined to one another by 8.39 (9)° and the mol-ecule has an E conformation about the C=C bond. In the crystal, mol-ecules stack head-to-tail along the b-axis direction. They are linked by very weak C-H⋯O contacts, forming C(4) chains along [100]. Two chains are linked by a pair of very weak C-H⋯O contacts, enclosing inversion-dimeric R 2 (2)(8) ring motifs. There are also C-H⋯π inter-actions present, which link the double-stranded chains, forming a two-dimensional network.

2-Di-phenyl-phosphanyl-1-methyl-1H-benzimidazole.

In the title compound, C20H18N2P, the P atom is bonded to the two phenyl and imidazole groups, with an average P-C bond length of 1.828 (2) Å. The three C-P-C bond angles have values consistent with a tetra-hedral geometry around the P atom with the fourth site occupied by a H atom. Crystal packing is through van der Waals inter-actions.

Synthesis, crystal structures, and dual donor luminescence sensitization in novel terbium tetracyanoplatinates.

A series of novel terbium tetracyanoplatinate compounds all incorporating tridentate 2,2':6'2″-terpyridine (terpy) or 4'-chloro-2,2':6'2″-terpyridine (terpy-Cl) were synthesized and used to investigate the phenomenon of dual-donor sensitization of Tb(3+). Judicious choice of the Tb(3+) salt and reaction conditions results in the isolation of {Tb(terpy)(H2O)2(NO3)Pt(CN)4}·CH3CN (1A), {Tb(terpy)(H2O)2(NO3)Pt(CN)4}·3.5H2O (1B), {Tb(terpy-Cl)(H2O)2(NO3)Pt(CN)4}·2.5H2O (2), [Tb(terpy)(H2O)2(CH3COO)2]2Pt(CN)4·4H2O (3), or [Tb2(terpy)2(H2O)2(CH3COO)5]2Pt(CN)4·7H2O (4). The compounds 1A, 1B, and 2 contain one-dimensional polymeric structures with bridging of [Tb(L)(NO3)(H2O)2](2+) (L = terpy or terpy-Cl) moieties by cis-bridging tetracyanoplatinate (TCP) anions as determined via single-crystal X-ray diffraction studies. Both 3 and 4, however, contain Tb(3+) coordinated by multiple acetate ligands and terpy, but not TCP, and are classified as zero-dimensional complex salts. Platinophilic interactions that dominate tetracyanoplatinate structural chemistry are present in the form of dimeric units in the polymeric compounds, but are totally absent in 3 and 4. The structural differences result in markedly different luminescence properties for the two classes of compounds. All of the polymeric compounds display efficient donor-acceptor intramolecular energy transfer (IET) from the terpy unit to the Tb(3+) ion. Although the TCP units are also directly coordinated to the Tb(3+) ion in the three polymers, only in 1B and 2 are the Pt···Pt interactions strong enough to provide MMLCT bands of appropriate energy to result in a dual-donor effect to the Tb(3+) sensitization. Even in these cases, TCP does not efficiently sensitize the Tb(3+), rather a broad band TCP emission results. However, terpy and acetate ligands are bonded directly to the Tb(3+) ion in 3 and 4 and provide a strong dual-donor sensitization effect as evidenced by the large QY for Tb(3+).

Synthesis, structural, and photoluminescence studies of Gd(terpy)(H2O)(NO3)2M(CN)2 (M = Au, Ag) complexes: multiple emissions from intra- and intermolecular excimers and exciplexes.

The highly luminescent bimetallic cyanide materials, Gd(terpy)(H(2)O)(NO(3))(2)M(CN)(2) (M = Au, Ag; GdAu and GdAg, respectively) are quick and easy to synthesize under ambient conditions. A characteristic feature exhibited by both solid-state compounds is an intense red emission when excited with UV light. Additionally, GdAu exhibits a broad-band green emission upon excitation in the near UV region. A combination of structural and spectroscopic results for the compounds helps explain the underlying conditions responsible for their unique properties. Single-crystal X-ray diffraction experiments expose their structural features, including the fact that they are isostructural. Crystallographic data for the representative GdAu compound (Mo K(α), λ = 0.71073 Å, T = 290 K): triclinic, space group P ̅1, a = 7.5707(3) Å, b = 10.0671(4) Å, c = 15.1260(4) Å, α = 74.923(3)°, ß = 78.151(3)°, γ = 88.401(3)°, V = 1089.04(7) Å(3), and Z = 2. Although the compounds crystallize as dimers containing M···M distances smaller than the sum of their van der Waals radii, the Au···Au (3.5054(4) Å) and/or the Ag···Ag (3.6553(5) Å) interactions are relatively weak and are not responsible for the low energy red emission. Rather, the green emission in GdAu presumably originates from the [Au(CN)(2)(-)](2) dimeric excimer, while the [Ag(CN)(2)(-)](2) dimers in GdAg do not display visible emission at either 290 or 77 K. The unusual red emission exhibited by both compounds likely originates from the formation of an excited state exciplex that involves intermolecular π-stacking of 2,2':6',2"-terpyridine ligands. The room-temperature and low-temperature steady-state photoluminescent properties, along with detailed time-dependent, lifetime, and quantum yield spectroscopic data provide evidence regarding the sources of the multiple visible emissions exhibited by these complexes.

Temporal and Spatial Patterns and a Space-Time Cluster Analysis of Foot-and-Mouth Disease Outbreaks in Ethiopia from 2010 to 2019.

Foot-and-mouth disease (FMD) is an endemic disease in Ethiopia, although space-time cluster and monthly variation studies have never been assessed at national level. The current study aimed to identify the spatial and temporal distribution of FMD outbreaks in Ethiopia from national outbreak reports over a period of ten years from 1 January 2010 to 31 December 2019. To this end, a total of 376,762 cases and 1302 outbreaks from 704 districts were obtained from the Minister of Agriculture for analyses. In general, the dry periods, i.e., October to March, of the year were recorded as the peak outbreak periods, with the highest prevalence in March 2012. The monthly average and the outbreak trends over ten years show a decrease of outbreaks from 2010 to 2019. Decomposing the FMD outbreak data time series showed that once an outbreak erupted, it continued for up to five years. Only 12% of the reported outbreaks were assigned to a specific serotype. Within these outbreaks, the serotypes O, A, SAT-2, and SAT-1 were identified in decreasing order of prevalence, respectively. When a window of 50% for the maximum temporal/space cluster size was set, a total of seven FMD clusters were identified in space and time. The primary cluster with a radius of 380.95 km was identified in the southern part of Ethiopia, with a likelihood ratio of 7.67 (observed/expected cases). The third cluster, with a radius of 144.14 km, was identified in the northeastern part of the country, and had a likelihood ratio of 5.66. Clusters 1 and 3 occurred from January 2017 to December 2019. The second cluster that occurred had a radius of 294.82 km, a likelihood ratio of 6.20, and was located in the central and western parts of Ethiopia. The sixth cluster, with a radius of 36.04 km and a likelihood ratio of 20.60, was set in southern Tigray, bordering Afar. Clusters 2 and 6 occurred in the same period, from January 2014 to December 2016. The fourth cluster in northern Tigray had a calculated radius of 95.50 km and a likelihood ratio of 1.17. The seventh cluster occurred in the north-central Amhara region, with a radius of 97 km and a likelihood ratio of 1.16. Clusters 4 and 7 occurred between January 2010 and December 2013. The spatiotemporal and cluster analysis of the FMD outbreaks identified in the context of the current study are crucial in implementing control, prevention, and a prophylactic vaccination schedule. This study pointed out October to March as well as the main time of the year during which FMD outbreaks occur. The area that extends from the south to north, following the central highlands, is the main FMD outbreak area in Ethiopia.

Solid-state photoluminescence sensitization of Tb3+ by novel Au2Pt2 and Au2Pt4 cyanide clusters.

The syntheses are reported for two novel Tb(3+) heterotrimetallic cyanometallates, K(2)[Tb(H(2)O)(4)(Pt(CN)(4))(2)]Au(CN)(2)·2H(2)O (1) and [Tb(C(10)N(2)H(8))(H(2)O)(4)(Pt(CN)(4))(Au(CN)(2))]·1.5C(10)N(2)H(8)·2H(2)O (2) (C(10)N(2)H(8) = 2,2'-bipyridine). Both compounds have been isolated as colorless crystals, and single-crystal X-ray diffraction has been used to investigate their structural features. Crystallographic data (MoKα, λ = 0.71073 Å, T = 290 K): 1, tetragonal, space group P4(2)/nnm, a = 11.9706(2) Å, c = 17.8224(3) Å, V = 2553.85(7) Å(3), Z = 4; 2, triclinic, space group P1, a = 10.0646(2) Å, b = 10.7649(2) Å, c = 17.6655(3) Å, α = 101.410(2)°, ß = 92.067(2)°, γ = 91.196(2)°, V = 1874.14(6) Å(3), Z = 2. For the case of 1, the structure contains Au(2)Pt(4) hexameric noble metal clusters, while 2 includes Au(2)Pt(2) tetrameric clusters. The clusters are alike in that they contain Au-Au and Au-Pt, but not Pt-Pt, metallophilic interactions. Also, the discrete clusters are directly coordinated to Tb(3+) and sensitize its emission in both solid-state compounds, 1 and 2. The Photoluminescence (PL) spectra of 1 show broad excitation bands corresponding to donor groups when monitored at the Tb(3+) ion f-f transitions, which is typical of donor/acceptor energy transfer (ET) behavior in the system. The compound also displays a broad emission band at ∼445 nm, assignable to a donor metal centered (MC) emission of the Au(2)Pt(4) clusters. The PL properties of 2 show a similar Tb(3+) emission in the visible region and a lack of donor-based emission at room temperature; however, at 77 K a weak, broad emission occurs at 400 nm, indicative of uncoordinated 2,2'-bipyridine, along with strong Tb(3+) transitions. The absolute quantum yield (QY) for the Tb(3+) emission ((5)D(4) → (7)F(J (J = 6-3))) in 1 is 16.3% with a lifetime of 616 µs when excited at 325 nm. In contrast the weak MC emission at 445 nm has a quantum yield of 0.9% with a significantly shorter lifetime of 0.61 µs. For 2 the QY value decreases to 9.3% with a slightly shorter lifetime of 562 µs. The reduced QY in 2 is considered to be a consequence of (1) the slightly increased donor-acceptor excited energy gap relative to the optimal gap suggested for Tb(3+) and (2) Tb(3+) emission quenching via a bpy ligand-to-metal charge transfer (LMCT) excited state.

Ethyl 5-oxo-2,3-diphenyl-cyclo-pentane-1-carboxyl-ate.

The title compound, C(20)H(20)O(3), was prepared by an acyl-oin-type condensation reaction in the presence of sodium sand and dry ether using ethyl cinnamate as the starting material. The C-O bond lengths for the carbonyl groups are 1.191 (2) and 1.198 (2) Å, while the C-O bond in the ester group is 1.335 (2) Å. The C-C bond lengths in the phenyl groups average 1.375 Å, while the C-C bonds in the cyclo-penta-none ring average 1.525 Å, indicating single C-C bonds in the latter.

Brucellosis in ruminants and pastoralists in Borena, Southern Ethiopia.

Brucellosis is a bacterial zoonotic disease that has important veterinary and public health consequences as well as economic impact in sub Saharan Africa including Ethiopia. A cross-sectional study was conducted in four selected districts of Borena Pastoral setting in Southern Ethiopia from October 2017 to February 2018 to estimate the prevalence of brucellosis and assess associated risk factors in cattle, sheep, goats and occupationally associated humans. A total of 750 cattle, 882 sheep and goats and 341 human subjects were screened for evidence of brucellosis using the Rose Bengal Test (RBT) with positive results confirmed by Competitive-ELISA(c-ELISA). Structured questionnaires were used for collection of metadata from individual animals, herders and animal attendants to test the association between explanatory and outcome variables. The overall animal level prevalence was 2.4% (95% confidence interval, CI: 1.4-3.7) in cattle, 3.2% (95% CI: 2.1-4.6) in sheep and goats, and 2.6% (95% CI: 1.2-5) in humans occupationally linked to livestock production systems. Herd size, parity, and history of abortion were risk factors associated with Brucella seropositivity (P<0.05) in cattle whereas in sheep and goats the results showed that district, age group, flock size, and history of abortion were significantly associated risk factors with Brucella seropositivity (P<0.05). Assisting calving and presence of seropositive animals in a household (P<0.05) were significantly associated with Brucella seropositivity in humans. Evidence of brucellosis in various animal species and the associated human population illustrates the need for a coordinated One Health approach to controlling brucellosis so as to improve public health and livestock productivity.

Emission enhancement through dual donor sensitization: modulation of structural and spectroscopic properties in a series of europium tetracyanoplatinates.

The synthesis of three different europium tetracyanoplatinates all incorporating 2,2':6',2''-terpyridine (terpy) have been carried out in acetonitrile/water mixtures by reaction of Eu(3+) salts with terpy and potassium tetracyanoplatinate. The use of different Eu(3+) sources results in the isolation of Eu(C(15)H(11)N(3))(H(2)O)(2)(NO(3))(Pt(CN)(4)) x CH(3)CN (1), {Eu(C(15)H(11)N(3))(H(2)O)(3)}(2)(Pt(CN)(4))(3) x 2 H(2)O (2), or [Eu(C(15)H(11)N(3))(H(2)O)(2)(CH(3)COO)(2)](2)Pt(CN)(4) x 3 H(2)O (3) for the nitrate, triflate, or acetate salts, respectively. All three compounds have been prepared as colorless crystals, and single-crystal X-ray diffraction has been used to investigate their structural features. Crystallographic data (MoK alpha, lambda = 0.71073 A, T = 290 K): 1, monoclinic, space group P2(1)/c, a = 12.835(1), b = 15.239(1), c = 13.751(2) A, beta = 105.594(9) degrees, V = 2590.8(5) A(3), Z = 4; 2, triclinic, space group P1, a = 9.1802(8) A, b = 10.8008(9) A, c = 13.5437(9) A, alpha = 84.491(6) degrees, beta = 75.063(7) degrees, gamma = 79.055(7) degrees, V = 1272.4(2) A(3), Z = 1; 3, triclinic, space group P1, a = 12.110(3) A, b = 12.7273(11) A, c = 18.7054(16) A, alpha = 92.859(7) degrees, beta = 92.200(11) degrees, gamma = 118.057(10) degrees, V = 2534.8(7) A(3), Z = 2. Variation of the counteranions in these systems provides the opportunity to modify the structures and coordination environment of Eu(3+) for 1-3. Compounds 1 and 2 are both one-dimensional, polymeric compounds that contain Eu(3+) ions chelated by terpy and bridged by tetracyanoplatinate anions. 3 is a zero-dimensional complex salt in which Eu(3+) is coordinated by terpy, acetate, and water, but not tetracyanoplatinate. The structural differences result in varying sensitization phenomena for the three compounds. Compounds 1 and 2 display efficient donor-acceptor intramolecular energy transfer (IET) where dual donor species, terpyridine and tetracyanoplatinate, simultaneously enhance the acceptor Eu(3+) emission. In both compounds the donor species are directly coordinated to the acceptor ion, and hence a highly efficient dual-donor effect is exhibited for the IET mechanisms. In 3 where only the terpy ligand is directly coordinated to Eu(3+), the sensitization involves only one donor species. The Pt(CN)(4)(2-) unit in 3, which lacks direct bonding to Eu(3+), exhibits strong emission indicating the lack of cooperative enhancement of the lanthanide emission.

Caspase-3-truncated type 1 inositol 1,4,5-trisphosphate receptor enhances intracellular Ca2+ leak and disturbs Ca2+ signalling.

BACKGROUND INFORMATION: The IP(3)R (inositol 1,4,5-trisphosphate receptor) is a tetrameric channel that accounts for a large part of the intracellular Ca(2+) release in virtually all cell types. We have previously demonstrated that caspase-3-mediated cleavage of IP(3)R1 during cell death generates a C-terminal fragment of 95 kDa comprising the complete channel domain. Expression of this truncated IP(3)R increases the cellular sensitivity to apoptotic stimuli, and it was postulated to be a constitutively active channel. RESULTS: In the present study, we demonstrate that expression of the caspase-3-cleaved C-terminus of IP(3)R1 increased the rate of thapsigargin-mediated Ca(2+) leak and decreased the rate of Ca(2+) uptake into the ER (endoplasmic reticulum), although it was not sufficient by itself to deplete intracellular Ca(2+) stores. We detected the truncated IP(3)R1 in different cell types after a challenge with apoptotic stimuli, as well as in aged mouse oocytes. Injection of mRNA corresponding to the truncated IP(3)R1 blocked sperm factor-induced Ca(2+) oscillations and induced an apoptotic phenotype. CONCLUSIONS: In the present study, we show that caspase-3-mediated truncation of IP(3)R1 enhanced the Ca(2+) leak from the ER. We suggest a model in which, in normal conditions, the increased Ca(2+) leak is largely compensated by enhanced Ca(2+)-uptake activity, whereas in situations where the cellular metabolism is compromised, as occurring in aging oocytes, the Ca(2+) leak acts as a feed-forward mechanism to divert the cell into apoptosis.

Laser spectroscopy for atmospheric and environmental sensing.

Lasers and laser spectroscopic techniques have been extensively used in several applications since their advent, and the subject has been reviewed extensively in the last several decades. This review is focused on three areas of laser spectroscopic applications in atmospheric and environmental sensing; namely laser-induced fluorescence (LIF), cavity ring-down spectroscopy (CRDS), and photoluminescence (PL) techniques used in the detection of solids, liquids, aerosols, trace gases, and volatile organic compounds (VOCs).

Glucocorticoids and checkpoint tyrosine kinase inhibitors stimulate rat pancreatic beta cell proliferation differentially.

Cell therapy for diabetes could benefit from the identification of small-molecule compounds that increase the number of functional pancreatic beta cells. Using a newly developed screening assay, we previously identified glucocorticoids as potent stimulators of human and rat beta cell proliferation. We now compare the stimulatory action of these steroid hormones to a selection of checkpoint tyrosine kinase inhibitors that were also found to activate the cell cycle-in beta cells and analyzed their respective effects on DNA-synthesis, beta cell numbers and expression of cell cycle regulators. Our data using glucocorticoids in combination with a receptor antagonist, mifepristone, show that 48h exposure is sufficient to allow beta cells to pass the cell cycle restriction point and to become committed to cell division regardless of sustained glucocorticoid-signaling. To reach the end-point of mitosis another 40h is required. Within 14 days glucocorticoids stimulate up to 75% of the cells to undergo mitosis, which indicates that these steroid hormones act as proliferation competence-inducing factors. In contrast, by correlating thymidine-analogue incorporation to changes in absolute cell numbers, we show that the checkpoint kinase inhibitors, as compared to glucocorticoids, stimulate DNA-synthesis only during a short time-window in a minority of cells, insufficient to give a measurable increase of beta cell numbers. Glucocorticoids, but not the kinase inhibitors, were also found to induce changes in the expression of checkpoint regulators. Our data, using checkpoint kinase-specific inhibitors further point to a role for Chk1 and Cdk1 in G1/S transition and progression of beta cells through the cell cycle upon stimulation with glucocorticoids.

Ultraviolet radiation-induced apoptosis in keratinocytes: on the role of cytosolic factors.

Epidemiological and experimental evidences have established solar ultraviolet (UV) radiation as the leading cause of skin cancers. Specifically, the frequency of non-melanoma skin cancer, one of the malignancies with the most rapidly increasing incidence, is directly related to the total exposure to solar UV light. As part of a general effort to elucidate the components of cellular signal transduction pathways, the mechanisms of cellular responses to UV radiation have received considerable attention over the last few years. These efforts were driven mainly by the conviction that understanding how normal cells respond to extracellular stimuli such as exposure to UV radiation will undoubtedly help in deciphering what goes wrong in a variety of clinical disorders including skin cancers and will assist in the development of novel therapeutic strategies. Studies over the last decade have established that UV radiation induces a bewildering array of signal transduction pathways, some of which could lead to apoptotic cell death. UV-induced cell death by apoptosis is considered to be a natural protective mechanism that removes damaged keratinocytes and circumvents the risk of malignant transformation. In this review, we summarize some of the most important findings regarding the response and role of mitogen-activated protein kinases in UVA and UVB radiation-induced signaling to apoptosis in keratinocytes. We will also briefly discuss what is known about the role of the BCL-2 family of proteins, the emerging role of lysosomal proteases and other important cytosolic signaling proteins in UV-induced apoptosis.

Crystal structure of bis-(1,3-di-amino-propane-κ(2) N,N')bis-[2-(4-nitro-phen-yl)acetato-κO]cadmium.

In the structure of the title compound, [Cd(C8H6NO4)2(C3H10N2)2], the Cd(II) atom is located on a center of symmetry with one independent Cd-O distance of 2.3547 (17) Šand two Cd-N distances of 2.3265 (18) and 2.3449 (19) Å. The Cd(II) atom has an overall octa-hedral coordination environment. Several types of hydrogen-bonding inter-actions are evident. Both intra- and inter-molecular inter-actions occur between the amino groups and the O atoms of the acetate group. These N-H⋯O hydrogen bonds lead to a layered structure extending parallel to the bc plane. In addition, weak inter-molecular C-H⋯O inter-actions involving the nitro groups exist, leading to the formation of a three-dimensional network structure.

Thimerosal stimulates Ca2+ flux through inositol 1,4,5-trisphosphate receptor type 1, but not type 3, via modulation of an isoform-specific Ca2+-dependent intramolecular interaction.

Thiol-reactive agents such as thimerosal have been shown to modulate the Ca2+-flux properties of IP3 (inositol 1,4,5-trisphosphate) receptor (IP3R) via an as yet unidentified mechanism [Parys, Missiaen, De Smedt, Droogmans and Casteels (1993) Pflügers Arch. 424, 516-522; Kaplin, Ferris, Voglmaier and Snyder (1994) J. Biol. Chem. 269, 28972-28978; Missiaen, Taylor and Berridge (1992) J. Physiol. (Cambridge, U.K.) 455, 623-640; Missiaen, Parys, Sienaert, Maes, Kunzelmann, Takahashi, Tanzawa and De Smedt (1998) J. Biol. Chem. 273, 8983-8986]. In the present study, we show that thimerosal potentiated IICR (IP3-induced Ca2+ release) and IP3-binding activity of IP3R1, expressed in triple IP3R-knockout R23-11 cells derived from DT40 chicken B lymphoma cells, but not of IP3R3 or [D1-225]-IP3R1, which lacks the N-terminal suppressor domain. Using a 45Ca2+-flux technique in permeabilized A7r5 smooth-muscle cells, we have shown that Ca2+ shifted the stimulatory effect of thimerosal on IICR to lower concentrations of thimerosal and thereby increased the extent of Ca2+ release. This suggests that Ca2+ and thimerosal synergetically regulate IP3R1. Glutathione S-transferase pull-down experiments elucidated an interaction between amino acids 1-225 (suppressor domain) and amino acids 226-604 (IP3-binding core) of IP3R1, and this interaction was strengthened by both Ca2+ and thimerosal. In contrast, calmodulin and sCaBP-1 (short Ca2+-binding protein-1), both having binding sites in the 1-225 region, weakened the interaction. This interaction was not found for IP3R3, in agreement with the lack of functional stimulation of this isoform by thimerosal. The interaction between the IP3-binding and transmembrane domains (amino acids 1-604 and 2170-2749 respectively) was not affected by thimerosal and Ca2+, but it was significantly inhibited by IP3 and adenophostin A. Our results demonstrate that thimerosal and Ca2+ induce isoform-specific conformational changes in the N-terminal part of IP3R1, leading to the formation of a highly IP3-sensitive Ca2+-release channel.

Crystal structure of tert-butyl-diphenyl-phosphine oxide.

In the structure of the title triorganophosphine oxide, C16H19OP, the P-O bond is 1.490 (1) Å. The P atom has a distorted tetrahedral geometry. The O atom inter-acts with both phenyl groups of a neighboring mol-ecule [C⋯O = 2.930 (3) and 2.928 (4) Å]. The C-O interaction directs an extended supramolecular arrangement along the a-axis.