BG Region Research Articles

The minor chicken class I gene BF1 is deleted between short imperfect direct repeats in the B14 and typical B15 major histocompatibility complex (MHC) haplotypes

The chicken major histocompatibility complex (MHC, also known as the BF-BL region of the B locus) is notably small and simple with few genes, most of which are involved in antigen processing and presentation. There are two classical class I genes, of which only BF2 is well and systemically expressed as the major ligand for cytotoxic T lymphocytes (CTLs). The other class I gene, BF1, is believed to be primarily a natural killer (NK) cell ligand. Among most standard chicken MHC haplotypes examined in detail, BF1 is expressed tenfold less than BF2 at the RNA level due to defects in the promoter or in a splice site. However, in the B14 and typical B15 haplotypes, BF1 RNA was not detected, and here, we show that a deletion between imperfect 32 nucleotide direct repeats has removed the BF1 gene entirely. The phenotypic effects of not having a BF1 gene (particularly on resistance to infectious pathogens) have not been systematically explored, but such deletions between short direct repeats are also found in some BF1 promoters and in the 5′ untranslated region (5′UTR) of some BG genes found in the BG region of the B locus. Despite the opposite transcriptional orientation of homologous genes in the chicken MHC, which might prevent the loss of key genes from a minimal essential MHC, it appears that small direct repeats can still lead to deletion.

Subthalamic Nucleus Deep Brain Stimulation Restores Motor and Sensorimotor Cortical Neuronal Oscillatory Activity in the Free-Moving 6-Hydroxydopamine Lesion Rat Parkinson Model

ObjectivesEnhanced beta oscillations in cortical-basal ganglia (BG) thalamic circuitries have been linked to clinical symptoms of Parkinson’s disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces beta band activity in BG regions, whereas little is known about activity in cortical regions. In this study, we investigated the effect of STN DBS on the spectral power of oscillatory activity in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) by recording via an electrocorticogram (ECoG) array in free-moving 6-hydroxydopamine (6-OHDA) lesioned rats and sham-lesioned controls. Materials and MethodsMale Sprague–Dawley rats (250–350 g) were injected either with 6-OHDA or with saline in the right medial forebrain bundle, under general anesthesia. A stimulation electrode was then implanted in the ipsilateral STN, and an ECoG array was placed subdurally above the MCtx and SMCtx areas. Six days after the second surgery, the free-moving rats were individually recorded in three conditions: 1) basal activity, 2) during STN DBS, and 3) directly after STN DBS. ResultsIn 6-OHDA-lesioned rats (N = 8), the relative power of theta band activity was reduced, whereas activity of broad-range beta band (12–30 Hz) along with two different subbeta bands, that is, low (12–30 Hz) and high (20–30 Hz) beta band and gamma band, was higher in MCtx and SMCtx than in sham-lesioned controls (N = 7). This was, to some extent, reverted toward control level by STN DBS during and after stimulation. No major differences were found between contacts of the electrode grid or between MCtx and SMCtx. ConclusionLoss of nigrostriatal dopamine leads to abnormal oscillatory activity in both MCtx and SMCtx, which is compensated by STN stimulation, suggesting that parkinsonism-related oscillations in the cortex and BG are linked through their anatomic connections.

Knowledge and Attitude Towards Family Planning Among Women of Reproductive Age in Emerging Regions of Ethiopia.

BackgroundDespite recent improvements in the use of contraceptives amongst married women in Ethiopia, the utilization rates are still far below the national figures in the emerging regions of the country. Therefore, there is a need to assess the level of knowledge and attitudes towards family planning, and associated factors among reproductive-age women in the four emerging regions of Ethiopia.MethodsA community-based cross-sectional study was conducted among 2891 reproductive-age women from 01 to 30 June, 2017. The data were collected by open data equipped tablets with kit software using structured questionnaire. The collected data were exported to STATA version 14 for analysis. Knowledge and attitude were assessed using tools containing 12 and 9 questions, respectively. Mean scores were used as cut-off points. Internal consistency of the tool was checked using Cronbach alpha coefficient, and it was 0.87 for knowledge and 0.78 for attitude questions. Bivariate and multivariate analyses were done, and statistical significance was declared at p-value ≤ 0.05.ResultsLess than half, 1254 (43.4%), of the participants had good knowledge and 1511 (52.3%) had favorable attitude towards FP. Positive predictors of good knowledge of family planning were: being from Benishangul-Gumuz region, urban residence, older age, high level of education, being Christian and merchant, high household monthly income, and listening/watching radio/TV. On the other hand, high family size and ideal desired children were negative predictors. For a favorable attitude, the positive predictors include older age, high level of partner education, listening/watching radio/TV, being from BG region and having a good knowledge of FP. Desiring high number of ideal children and being a student by occupation were negatively associated with a favorable attitude.ConclusionThe study revealed that significant number of women had poor knowledge and attitude towards FP. Multiple socio-demographic factors contributed to knowledge and attitude of FP. Therefore, the health sectors of the regions and other stakeholders should strengthen the health extension program to disseminate messages related to FP to improve the knowledge and attitude of women.

Evaluation of Post-reconstruction Filtering in Resolution Recovery Reconstruction for Bone SPECT Imaging

The aim of this study was to clarify the optimal post-reconstruction filtering type in the three- dimensional ordered subset expectation maximization (3D-OSEM) method for bone single photon emission computed tomography (SPECT) from image quality and quantitative values. We scanned a National Electrical Manufactures Association's body phantom for bone SPECT filled with radioactive solution of 99mTc whose radioactivity concentration was accurately measured. The SPECT images were created using the 3D-OSEM method. Post-reconstruction filtering was performed using a Butterworth filter (BW), a Gaussian filter (GA), and a Hanning filter (HA) with various parameters. The image quality was evaluated by the normalized mean-squared error (NMSE) value and % of contrast-to-noise ratio (QNR17). The image quality was evaluated by the error values between the measured radioactivity concentration and the true radioactivity concentration in the BG region and insert sphere. The minimum NMSE values were 0.034 (BW), 0.036 (GA), and 0.035 (HA), and there was no difference depending on the filter type. The values of QNR17 were 2.5 (BW), 2.6 (GA), and 2.6 (HA), and there was no difference depending on the filter type. The BG region was greatly affected by parameter changes in GA but less by those in BW and HA. The error values of the 37 mm insert sphere were 18.0% (BW), 28.2% (GA), and 26.2% (HA), and BW showed the lowest value. Our results suggest that the post-reconstruction filtering type used in the 3D-OSEM method was BW from the image quality and quantitative values.

Enlarged Perivascular Spaces and Cerebral Small Vessel Disease in Spontaneous Intracerebral Hemorrhage Patients.

Background: Cerebral small vessel disease (SVD) is associated with cognitive decline, depression, increased mortality, and disability in stroke patients. MRI-visible perivascular spaces (PVS) are a sensitive neuroimaging marker of SVD. We aimed to explore the risk factors and associations with other SVD markers of PVS in two topographical regions (in the basal ganglia [BG] and centrum semiovale [CS]) in a cohort of spontaneous intracerebral hemorrhage (ICH) patients.Method: We included 306 consecutive patients from a prospective spontaneous ICH cohort. We rated PVS, white matter hyperintensities (WMH), cerebral microbleeds (CMB), and lacunes with validated visual rating scale. We collected clinical information using standardized forms. We predefined severe PVS as score > 2 and examined associations between PVS in both BG and CS regions and clinical and imaging markers of SVD by logistic regression.Results: In the multivariable logistic regression, increasing age (OR = 1.075; 95% CI = 1.038–1.113, p < 0.001), high CS PVS degrees (OR = 6.906; 95% CI = 3.024–15.774, p < 0.001), extensive periventricular WMH (OR = 2.878; 95% CI = 1.298–6.379, p = 0.009), and the presence of CMB (OR = 4.073, 95% CI = 1.869–8.877, p < 0.001) were independently associated with BG PVS severity. Alcohol-drinking habit (OR = 2.805; 95% CI = 1.451–5.422, p = 0.002), hyperlipidemia history (OR = 3.782; 95% CI = 1.582–8.783, p = 0.003), high BG PVS degrees (OR = 6.293; 95% CI = 2.755–14.371, p < 0.001) and the presence of strictly lobar CMB (OR = 2.556, 95% CI = 1.285–5.085, p = 0.008) were independent predictors of increased CS PVS severity.Conclusion: MRI-visible PVS in BG and CS regions are inter-related and have different risk factors in spontaneous ICH patients. Further studies are needed to explore the mechanism and clinical importance of PVS, with possible implications for cerebrovascular disease prevention and effective treatments.

Functional Alleles of Chicken BG Genes, Members of the Butyrophilin Gene Family, in Peripheral T Cells.

γδ T cells recognize a wide variety of ligands in mammals, among them members of the butyrophilin (BTN) family. Nothing is known about γδ T cell ligands in chickens, despite there being many such cells in blood and lymphoid tissues, as well as in mucosal surfaces. The major histocompatibility complex (MHC) of chickens was discovered because of polymorphic BG genes, part of the BTN family. All but two BG genes are located in the BG region, oriented head-to-tail so that unequal crossing-over has led to copy number variation (CNV) as well as hybrid (chimeric) genes, making it difficult to identify true alleles. One approach is to examine BG genes expressed in particular cell types, which likely have the same functions in different BG haplotypes and thus can be considered “functional alleles.” We cloned nearly full-length BG transcripts from peripheral T cells of four haplotypes (B2, B15, B19, and B21), and compared them to the BG genes of the B12 haplotype that previously were studied in detail. A dominant BG gene was found in each haplotype, but with significant levels of subdominant transcripts in three haplotypes (B2, B15, and B19). For three haplotypes (B15, B19, and B21), most sequences are closely-related to BG8, BG9, and BG12 from the B12 haplotype. We found that variation in the extracellular immunoglobulin-variable-like (Ig-V) domain is mostly localized to the membrane distal loops but without evidence for selection. However, variation in the cytoplasmic tail composed of many amino acid heptad repeats does appear to be selected (although not obviously localized), consistent with an intriguing clustering of charged and polar residues in an apparent α-helical coiled-coil. By contrast, the dominantly-expressed BG gene in the B2 haplotype is identical to BG13 from the B12 haplotype, and most of the subdominant sequences are from the BG5-BG7-BG11 clade. Moreover, alternative splicing leading to intron read-through results in dramatically truncated cytoplasmic tails, particularly for the dominantly-expressed BG gene of the B2 haplotype. The approach of examining “functional alleles” has yielded interesting data for closely-related genes, but also thrown up unexpected findings for at least one haplotype.

Combined Diffusion Tensor and Magnetic Resonance Spectroscopic Imaging Methodology for Automated Regional Brain Analysis: Application in a Normal Pediatric Population

During human brain development, anatomic regions mature at different rates. Quantitative anatomy-specific analysis of longitudinal diffusion tensor imaging (DTI) and magnetic resonance spectroscopic imaging (MRSI) data may improve our ability to quantify and categorize these maturational changes. Computational tools designed to quickly fuse and analyze imaging information from multiple, technically different datasets would facilitate research on changes during normal brain maturation and for comparison to disease states. In the current study, we developed a complete battery of computational tools to execute such data analyses that include data preprocessing, tract-based statistical analysis from DTI data, automated brain anatomy parsing from T1-weighted MR images, assignment of metabolite information from MRSI data, and co-alignment of these multimodality data streams for reporting of region-specific indices. We present statistical analyses of regional DTI and MRSI data in a cohort of normal pediatric subjects (n = 72; age range: 5-18 years; mean 12.7 ± 3.3 years) to establish normative data and evaluate maturational trends. Several regions showed significant maturational changes for several DTI parameters and MRSI ratios, but the percent change over the age range tended to be small. In the subcortical region (combined basal ganglia [BG], thalami [TH], and corpus callosum [CC]), the largest combined percent change was a 10% increase in fractional anisotropy (FA) primarily due to increases in the BG (12.7%) and TH (9%). The largest significant percent increase in N-acetylaspartate (NAA)/creatine (Cr) ratio was seen in the brain stem (BS) (18.8%) followed by the subcortical regions in the BG (11.9%), CC (8.9%), and TH (6.0%). We found consistent, significant (p < 0.01), but weakly positive correlations (r = 0.228-0.329) between NAA/Cr ratios and mean FA in the BS, BG, and CC regions. Age- and region-specific normative MR diffusion and spectroscopic metabolite ranges show brain maturation changes and are requisite for detecting abnormalities in an injured or diseased population.

Genetic diversity analysis of the major histocompatibility complex (MHC) region in Indian native chicken breeds and pureline chickensusing the LEI0258 microsatellite marker

The chicken major histocompatibility complex (MHC) plays an important role in immune response and is strongly associated with resistance and susceptibility to many diseases. The microsatellite marker LEI0258 is physically located within MHC, between the BG and BF regions and can identify serologically well-defined MHC haplotypes. In the present study, a total of 150 samples from pureline chicken breeds including Indian native chicken breeds Aseel (20), Kadaknath (45), White Leghorn (IWI-20; IWK-23), Dahlem red (DR-20), Broiler (PB1-22) was investigated by using LEI0258 microsatellite marker. Overall 22 differently sized alleles (182-552 bp) were identified in all the five lines. Our results indicate that Indian native chicken breeds Aseel (Na=10) and Kadaknath (Na=11) harbored more alleles compared to those of pureline populations (Na=5-6). Analysis of Hardy-Weinberg’s equilibrium (HWE) revealed that two populations IWI and Kadaknath deviated from the HWE (P less than 0.001). LEI0258 microsatellite based MHC haplotyping would be useful in selecting birds for breeding programs and also in genetic resource conservation.

Different modes of variation for each BG lineage suggest different functions.

Mammalian butyrophilins have various important functions, one for lipid binding but others as ligands for co-inhibition of αβ T cells or for stimulation of γδ T cells in the immune system. The chicken BG homologues are dimers, with extracellular immunoglobulin variable (V) domains joined by cysteines in the loop equivalent to complementarity-determining region 1 (CDR1). BG genes are found in three genomic locations: BG0 on chromosome 2, BG1 in the classical MHC (the BF-BL region) and many BG genes in the BG region just outside the MHC. Here, we show that BG0 is virtually monomorphic, suggesting housekeeping function(s) consonant with the ubiquitous tissue distribution. BG1 has allelic polymorphism but minimal sequence diversity, with the few polymorphic residues at the interface of the two V domains, suggesting that BG1 is recognized by receptors in a conserved fashion. Any phenotypic variation should be due to the intracellular region, with differential exon usage between alleles. BG genes in the BG region can generate diversity by exchange of sequence cassettes located in loops equivalent to CDR1 and CDR2, consonant with recognition of many ligands or antigens for immune defence. Unlike the mammalian butyrophilins, there are at least three modes by which BG genes evolve.

Sequence of a complete chicken BG haplotype shows dynamic expansion and contraction of two gene lineages with particular expression patterns.

Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC), and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region), and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells), correlating with two different kinds of promoters and 5′ untranslated regions (5′UTR). However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.

White matter lesions and depression in patients with Parkinson's disease

Depression is frequently associated with Parkinson disease (PD) but neural basis is still unclear. In previous studies white matter changes present as signal hyperintesities on T2-wighted MRI studies (WMHs) commonly observed in older adults have been associated with depressive symptomatology. In this study we investigated whether WMHs were associated with depression in PD patients with disease onset above the age of 60. Thirty-four patients, with (PD-D) and 25 without depression (PD-nD), and 30 healthy age- and sex-matched controls were analyzed using the Scheltens visual rating scale. Cerebrovascular risk factors were similar across groups. Comparing controls and PD patients as a group there were no differences in WMHs in any examined regions. However, PD-D group had more common frontal WMHs although WMHs score didn't rich statistical significance. The same came true for total deep white matter changes comparing those two groups. In addition PD-D group had a significantly higher score for periventricular regions WMHs comparing with both PD-nD group and controls.PD-D group had significantly higher WMHs scores BG regions when compared to controls. The only significance in multivariate analyses was shown for periventricular WMHs total score explaining the 39% of the variance in the depressive score. Our findings suggest that WMH in the deep white matter may contribute to depression in PD.

Rous sarcoma growth in lines congenic for major histocompatibility (B) complex recombinants

Rous sarcoma virus (RSV)-induced tumor growth was examined in congenic lines of chickens with different major histocompatibility (B) complex recombinant haplotypes on the highly inbred line UCD 003 (B17B17) genetic background. Males bearing an individual B complex recombinant were mated to UCD 003 females followed by 10 backcross generations. Matings among heterozygotes for each recombinant produced homozygous chickens estimated to contain 99.9% of the line UCD 003 background genome. The 5 lines having distinct serologically identified MHC recombinant haplotypes, which arose from separate recombinational events, were as follows: 003.R1, 003.R2, 003.R4, 003. R5, and 003.R6. Chicks from each of the recombinant lines were challenged with 10 pfu subgroup A RSV at 6 wk of age. Tumors were scored for size 6 times over 10 wk postinoculation. Each bird was assigned a tumor profile index (TPI) based on the 6 tumor size scores. Hatch and B genotype were main effects in the statistical analysis. Least squares ANOVA was used to evaluate rank-transformed TPI values and mean tumor sizes through a repeated measures design. Tumor growth and TPI values were greater for 003.R1 and 003.R4 chickens than for the other 3 congenic lines. Among serologically similar recombinants 003.R2 and 003.R4, higher tumor growth and TPI in 003.R4 indicate unique genetic variation affecting RSV tumors compared with 003.R2. The similar tumor growth of 003.R5 and 003.R6 chickens, which have BF/BL21 but different BG regions, demonstrated no BG effect on RSV tumors.

Atom-like behaviors and orbital-related Tomonaga–Luttinger liquids in carbon nano-peapod quantum dots

We report ballistic charge transport phenomena observed in carbon nano-peapod quantum dots. We find atom-like behaviors (shell filling) sensitive to applied back-gate voltages (Vbg) by single electron spectroscopy. Doubly degenerate electronic levels are found only around ground states at very low Vbg. Those correlations with the presence of nearly free electron states unique to the peapods are discussed. Moreover, we find power laws in conductance versus energy relationships with anomalously high values of power, which are strongly associated with shell filling to the doubly degenerate levels. It is investigated that the powers originate from Tomonaga–Luttinger liquid via the occupied doubly degenerate levels. These results imply that a ballistic charge transport is still preserved at low-Vbg regions in carbon nano-peapod quantum dots in spite of the presence of the encapsulated C60 molecules.

Molecular genotype identification of the Gallus gallus major histocompatibility complex

The chicken major histocompatibility complex (MHC) is commonly defined by serologic reactions of erythrocytes with antibodies specific to the highly polymorphic MHC class I (BF) and MHC class IV (BG) antigens. The microsatellite marker LEI0258 is known to be physically located within the MHC, between the BG and BF regions. DNA from various serologically defined MHC haplotypes was amplified by polymerase chain reaction with primers surrounding this marker. Twenty-six distinctive allele sizes were identified. Some serologically well-defined MHC haplotypes shared a common LEI0258 allele size but could be distinguished either by the addition of information from another nearby marker (MCW0371) or by small indels or single nucleotide polymorphism (SNP) differences between the alleles. The association between LEI0258 allele and serologically defined MHC haplotype was very consistent for the same haplotype from multiple sources. Sequence information for the region defined by LEI0258 was obtained for 51 different haplotypes. Two internal repeats whose lengths were 13 and 12 bp, respectively, are the primary basis for allelic variability. Allele size variation ranges from 182 to 552 bp. Four indels and five SNPs in the surrounding sequence provide additional means for distinguishing alleles. Typing with LEI0258 and MCW0371 will be useful in identifying MHC haplotypes in outbred populations of chickens particularly for the initial development of serological reagents.

Is the gas supply market a natural monopoly? Econometric evidence from the British Gas regions

We have estimated a multi-output model of marketing and customer accounting costs in the BG regions. The cost function is well-behaved, separable, exhibits unitary elasticities of substitution between factor inputs and there are constant returns to scale when both outputs rise by the same proportion. When one output is held fixed, economies of scale can be exploited by expanding the other output. If our model is representative of the global cost function, this suggests that suppliers who already have a large market share in the non-domestic market will have a competitive advantage when the domestic market is liberalised in 1998.

95/00290 Natural gas industry transformation, competitive institutions and the role of regulation. Lessons from open access in US natural gas markets

We have estimated a multi-output model of marketing and customer accounting costs in the BG regions. The cost function is well-behaved, separable, exhibits unitary elasticities of substitution between factor inputs and there are constant returns to scale when both outputs rise by the same proportion. When one output is held fixed, economies of scale can be exploited by expanding the other output. If our model is representative of the global cost function, this suggests that suppliers who already have a large market share in the non-domestic market will have a competitive advantage when the domestic market is liberalised in 1998.

Influence of different B-complex recombinants on the outcome of Rous sarcomas in chickens.

Seven major histocompatibility (B) complex recombinants were evaluated for anti-Rous sarcoma response. In experiment 1, the BR5(F21-G19) recombinant haplotype both homozygous and in heterozygous combinations with B19 and B21 haplotypes were compared to B19/B19 and B21/B21 chickens to determine the relative influence of the BF versus BG chromosomal segments on regression of Rous sarcoma virus-induced tumours. In experiment 2, six recombinant haplotypes BR1(F24-G23), BR2(F2-G23), BR3(F2-G23), BR4(F2-G23), BR6(F21-G23) and BR8(F2-G2a,23) present in chickens heterozygous for normal haplotypes B19, B23 or B26 were compared for anti-sarcoma response. A total of 1328 chickens were blood typed for B alloantigens at 17 days of age, inoculated in the wingweb with Rous sarcoma virus at 6 weeks and monitored for anti-tumour immune response over a 10-week period. Genotypes which shared the same BF haplotype, but differed in their BG regions, had similar anti-tumour responses, implicating the BF but not the BG region in tumour regression. Chickens carrying BF2 or BF21 had a strong anti-tumour response, while BF24 conferred a weaker response, regardless of the accompanying normal haplotype.