Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclic Di-GMP Receptor PlzA Controls Virulence Gene Expression through RpoS in Borrelia burgdorferi

ABSTRACT As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two two-component signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.
Genetic complexity and gametocyte production of Plasmodium falciparum in Fulani and Mossi communities in Burkina Faso

We have examined Plasmodium falciparum gametocyte prevalence, density and their genetic complexity among children of 2 sympatric ethnic groups (Mossi and Fulani) in villages in Burkina Faso. The 2 groups are known to have distinct differences in their susceptibility and immune responses to malaria. We used RT-PCR and sequence-specific probes to detect and type RNA of the gametocyte-specific protein Pfs48/45. There were no differences in detection rates of asexual forms and gametocytes among the 2 groups, using PCR and RT-PCR, respectively. However, there were significant differences in densities of asexual forms and gametocytes, which were both higher among Mossi than Fulani. Both asexual forms and gametocyte densities were influenced by age and ethnicity. Multiple-clone infections with more than 1 gametocyte genotype were equally prevalent among Fulani and Mossi. These differences can most probably be attributed to genetic differences in malaria susceptibility in the 2 ethnic groups.
Comparative sensitivity of indirect immunofluorescence to immunoblot assay for the detection of circulating antibodies to bullous pemphigoid antigens 1 and 2

Summary The sera of 263 patients with bullous pemphigoid (BP) were tested by indirect immunofluorescence (IIF) on salt‐split skin (SSS) and immunoblot (IB) assay, in order to assess the diagnostic sensitivity of these techniques. Among the 263 sera tested. 198 sera (75%) contained antibasement membrane zone antibodies demonstrable by IIF reacting to the epidermal (98%) or both the dermal and epidermal sides (2%) of SSS. One hundred and eighty‐two of the 263 sera (69%) reacted by IB with BP antigens (Ag), most commonly the BPAgl (93 cases, 51%), and a complex of BPAgl and the 180kDa minor BP antigen (BPAg2) (47 cases, 26%). BPAg2 alone was found in 42 cases (23%). A good correlation was found between the detection of autoantibodies by IIF and labelling of BPAg1 and/or BPAg2 by IB assay, in which 152 of 198 sera with an epidermal pattern in IIF identified a BP antigen. IB analysis of the 65 sera negative by IIF yielded positive results in 30 cases (46%). Thirty‐one per cent (13 of 42) of sera recognizing by IB BPAg2, were negative by IIF, as compared with 12% (11 of 93) of those recognizing BPAg1 (P < 0.01). Comparing the sensitivity of the two tests, IIF (75%) was found to be more sensitive than IB (69%). Thirty‐five of the 263 sera (13%) remained negative by both techniques. It can be concluded from this study that IIF on SSS appears to be a sensitive and reliable assay for screening BP;IB should be performed for the sera that are negative by IIF as it may reveal circulating antibodies, particularly to BPAg2.
Enhanced Inhibition of Orthopoxvirus Replication In Vitro by Alkoxyalkyl Esters of Cidofovir and Cyclic Cidofovir

ABSTRACT The nucleotide phosphonates cidofovir (CDV) and cyclic cidofovir (cCDV) are potent antiviral compounds when administered parenterally but are not well absorbed orally. These compounds have been reported to have activity against orthopoxvirus replication in vitro and in animal models when administered parenterally or by aerosol. To obtain better oral activity, we synthesized a novel series of analogs of CDV and cCDV by esterification with two long-chain alkoxyalkanols, 3-hexadecyloxy-1-propanol (HDP-CDV; HDP-cCDV) or 3-octadecyloxy-1-ethanol (ODE-CDV; ODE-cCDV). Their activities were evaluated and compared with those of CDV and cCDV in human foreskin fibroblast (HFF) cells infected with vaccinia virus (VV) or cowpox virus (CV) using a plaque reduction assay. The 50% effective concentrations (EC50s) against VV in HFF cells for CDV and cCDV were 46.2 and 50.6 μM compared with 0.84 and 3.8 μM for HDP-CDV and HDP-cCDV, respectively. The EC50s for ODE-CDV and ODE-cCDV were 0.20 and 1.1 μM, respectively. The HDP analogs were 57- and 13-fold more active than the parent nucleotides, whereas the ODE analogs were 231- and 46-fold more active than the unmodified CDV and cCDV. Similar results were obtained using CV. Cytotoxicity studies indicated that although the analogs were more toxic than the parent nucleotides, the selective index was increased by 4- to 13-fold. These results indicate that the alkoxyalkyl esters of CDV and cCDV have enhanced activity in vitro and need to be evaluated for their oral absorption and efficacy in animal models.
Descriptive epidemiological study on culling and deaths in eight dairy herds.

OBJECTIVES To describe the production and reproduction characteristics of the population under investigation and to compare them with the target population of non-seasonally calving dairy herds, to describe the pattern of culling with respect to length of productive life and length of time after calving, and to identify stages of the production cycle that are associated with increased risk of culling from the dairy herd. DESIGN A longitudinal population study of eight non-seasonally calving dairy herds in the Camden district of New South Wales. RESULTS The production and reproduction characteristics of this population were broadly similar to herds participating in the New South Wales Agriculture Dairy Herd Improvement scheme. In agreement with recent surveys, risk of culling increased with increased parity. This was accounted for specifically by increased risk of culling for calving disorders, reproductive tract lesions, and disorders of the udder. Risk of culling for failure to conceive appeared to remain constant throughout productive life. The overall risks for culling were greatest during the first 9 days after calving and 300 days after calving. CONCLUSION Reducing the incidence of calving-associated disorders, attention to reproductive management and control of herd mastitis offer opportunities to reduce involuntary culling rates in this population.
Plasma Homocysteine Levels in Indian Patients with Essential Hypertension and Their Siblings

Background. An association between plasma homocysteine and essential hypertension and their non-hypertensive siblings is controversial. Methods and Results. Plasma homocysteine levels were measured in subjects with essential hypertension (n = 50), their normotensive siblings (n = 50) and normotensive controls (n = 50). All the subjects were non-diabetic, had no past history of myocardial infarction, stroke or peripheral vascular disease and had normal renal functions. The mean homocysteine values were 18.96 ± 8.08 µmol/L in patients, 14.84 ± 5.55 µmol/L in siblings and 10.50 ± 4.92 µmol/L in controls. Plasma homocysteine level were found to be significantly higher in patients with hypertension (p < 0.0001) and their normotensive siblings (p<0.0001) when compared to controls. Also patients with hypertension had their higher plasma homocysteine levels compared to their siblings (p<0.0036). Conclusion. Plasma homocysteine levels are significantly elevated in Indian patients with essential hypertension and their normotensive siblings. Thus, plasma homocysteine may serve as a marker for the development of essential hypertension.
Control of ventilation in elite synchronized swimmers.

Synchronized swimmers perform strenuous underwater exercise during prolonged breath holds. To investigate the role of the control of ventilation and lung volumes in these athletes, we studied the 10 members of the National Synchronized Swim Team including an olympic gold medalist and 10 age-matched controls. We evaluated static pulmonary function, hypoxic and hypercapnic ventilatory drives, and normoxic and hyperoxic breath holding. Synchronized swimmers had an increased total lung capacity and vital capacity compared with controls (P less than 0.005). The hypoxic ventilatory response (expressed as the hyperbolic shape parameter A) was lower in the synchronized swimmers than controls with a mean value of 29.2 +/- 2.6 (SE) and 65.6 +/- 7.1, respectively (P less than 0.001). The hypercapnic ventilatory response [expressed as S, minute ventilation (1/min)/alveolar CO2 partial pressure (Torr)] was no different between synchronized swimmers and controls. Breath-hold duration during normoxia was greater in the synchronized swimmers, with a mean value of 108.6 +/- 4.8 (SE) vs. 68.03 +/- 8.1 s in the controls (P less than 0.001). No difference was seen in hyperoxic breath-hold times between groups. During breath holding synchronized swimmers demonstrated marked apneic bradycardia expressed as either absolute or heart rate change from basal heart rate as opposed to the controls, in whom heart rate increased during breath holds. Therefore the results show that elite synchronized swimmers have increased lung volumes, blunted hypoxic ventilatory responses, and a marked apneic bradycardia that may provide physiological characteristics that offer a competitive advantage for championship performance. (ABSTRACT TRUNCATED AT 250 WORDS)
Discordance of spatial representation in ensembles of hippocampal place cells

The extent to which small ensembles of neighboring hippocampal neurons alter their spatial firing patterns concurrently in response to stimulus manipulations was examined in young adult rats as well as in aged rats with and without memory impairment. Recordings from CA1 and CA3 cells were taken as rats performed a spatial radial‐maze task that employed prominent distal visual stimuli attached to dark curtains surrounding the maze and local cues on each maze arm provided by inserts with distinctive visual, tactile, and olfactory stimuli. To test the influence of the different stimulus subsets, the distal and local cues were rotated 90° in opposite directions (a Double Rotation). In response to this manipulation, place fields could maintain a fixed position to room coordinates, rotate with either the local or the distal cues, disappear, or new fields could appear. On average 79% of the cells within an ensemble responded in the same way, but only 37% of all ensembles were fully concordant. Typically discordant ensembles had place fields that rotated with one set of cues, whereas the other fields disappeared or new fields appeared. Ensembles in which the place fields rotated in two opposite directions were less frequent in young rats than would be expected by the occurrence of the individual responses, indicating selective competition between directly conflicting representations and ultimate suppression of one. These findings indicate that hippocampal neurons independently encode distinct subsets of the cues in a complex environment, although processing within the hippocampal network may actively reduce the simultaneous representation of conflicting orientation information. This kind of population activity might reflect the higher‐order organization of new memories within an established knowledge framework or schema.
Management and Point-of-Care for Tobacco Dependence (PROMPT): a feasibility mixed methods community-based participatory action research project in Ottawa, Canada

Objective To determine the feasibility of a Community-Based Participatory Tobacco Dependence Strategy (PROMPT) in the inner city population of Ottawa (Canada). Design A feasibility mixed methods prospective cohort study following principles of community-based participatory action research. Intervention Recruited 80 people whouse drugs, followed them for 6 months while providing access to counselling, nicotine replacement therapy and peer-support in a community setting. Setting Community research office in downtown Ottawa, adjacent to low-income housing, shelter services and street-based drug consumption. Primary outcome Retention rate at 6-month follow-up. Secondary outcome Biochemically validated 7-day point prevalence smoking abstinence at 26 weeks, self-reported abstinence in the past 7 days with exhaled carbon monoxide ≤10 ppm. Results The average age of participants was 43.8 years. The 6-month follow-up rate was 42.5%. The mean number of smoking years reported was 27.3 years. The participants were 70% male, 33.7% reported less than a high-school education, 21% identified as indigenous and 43.8% reported an income between US$1000 and US$1999 per month. The baseline mean daily cigarette use was 20.5 and 9.3 cigarettes at study end, with mean reduction of 11.2 cigarettes at 6 months (P=0.0001). There was a considerable reduction in self-reported illicit substance use (18.8%), including a reduction in the opioids heroin (6.3%), fentanyl (2.6%) and Oxycontin (3.8%). The study findings also reveal psycho-socioeconomic benefits such as improved health, return to work and greater community engagement. Conclusions The PROMPT project describes socioeconomic variables associated with tobacco and polysubstance use. A programme focused on tobacco dependence, easily accessible in the community and led by community peers with lived experience is feasible to implement and has the potential to support positive life changes. PROMPT’s patient engagement model is an effective harm-reduction strategy for the growing opioid use crisis and can improve the health outcomes of marginalised at-risk populations worldwide.
Estradiol-Induced Estrogen Receptor-α Trafficking

Estradiol has rapid actions in the CNS that are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca2+]i) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERα has an extracellular portion. In addition to the full-length ERα [apparent molecular weight (MW), 66 kDa], surface biotinylation labeled an ERα-immunoreactive protein (MW, ∼52 kDa) identified by both COOH- and NH2-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 and 52 kDa ERα. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24–48 h reduced ERα levels, suggesting receptor downregulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERα–mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERα trafficking to and from the membrane. Estradiol-induced [Ca2+]i flux was also significantly increased at the time of peak ERα activation/internalization. These results demonstrate that ERα is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERα are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERα to augment and then terminate membrane-initiated signaling.
Hepatitis B birth dose vaccination rates among children in Beijing: A comparison of local residents and first and second generation migrants

ABSTRACT Providing hepatitis B vaccine to all neonates within 24 hours of birth (Timely Birth Dose, TBD) is the key preventative measure to control perinatal hepatitis B virus infection. Previous Chinese studies of TBD only differentiated between migrant and non-migrant (local-born generation-LG) children. Our study is the first to stratify migrants in Beijing into first generation migrants (FGM) and second generation migrants (SGM). Based on a questionnaire survey of 2682 people in 3 Beijing villages, we identified 283 children aged 0–15 years, from 246 households, who were eligible for a TBD. Multinomial logistic regression and statistical analyses were used to examine factors explaining TBD rates for LG, FGM and SGM children. Surprisingly, the TBD for LG Beijing children was not significantly different from migrant children. But after stratifying migrant children into FGM and SGM, revealed significant TBD differences were revealed across LG, FGM and SGM according to domicile (p-value < 0.001, OR = 3.24), first vaccination covered by government policy (p-value < 0.05, OR = 3.24), mother's knowledge of hepatitis B (p-value < 0.05, OR = 1.01) and the government's HBV policy environment (p-value < 0.05, OR = 2.338). Birthplace (p-value = 0.002, OR = 6.21) and better policy environments (p-value = 0.01, OR = 2.80) were associated with higher TBD rate for LG and SGM children. Compared with FGM children, SGM had a significantly poorer TBD rate (Fisher exact test of chi-square = 0.013). We identified SGM as a special risk group; proposed Hukou reform to improve SGM TBD; and called for Beijing health authorities to match TBD rates in other provinces, especially by improving practices by health authorities and knowledge of parents.
HIV testing and receipt of test results among homeless persons with serious mental illness.

OBJECTIVE The purpose of this study was to determine the rates and predictors of HIV testing and receipt of results among homeless adults with serious mental illness in the initial 3-month period after contact with a community-based case management program. METHOD Baseline and follow-up interview data came from clients (N=5,890) in the Access to Community Care and Effective Services and Supports program, an 18-site, 5-year federally sponsored demonstration designed to evaluate the effect of service system integration on outcomes for homeless persons with serious mental illness. RESULTS Overall, 38.0% of clients were tested for HIV in the 3 months after program entry; of these, 88.8% returned to receive their test results. Likelihood of being tested was independently associated with having been tested before, more severe psychiatric symptoms and drug problems, level of worry about getting AIDS, younger age, less education, minority status, longer-term homelessness, being sexually assaulted, being arrested, and health services utilization. Among those tested, likelihood of receiving the test results was higher among those with a history of prior testing and return for results, a higher frequency of testing, and more years of education and lower among those with drug abuse problems, outpatient medical service utilization, disability, and sexually transmitted disease. Interaction analyses showed that, for men, greater social support increased the likelihood of both HIV testing and receipt of results, while sexual victimization during follow-up decreased the likelihood that men would return for their HIV results. CONCLUSIONS The majority of homeless clients enrolled in an intensive case management program were not tested for HIV during the 3-month period after program entry. Among those tested, however, nearly 90% reported receiving their results. The findings may enhance the development and targeting of strategies to increase testing and awareness of HIV serostatus among high-risk mentally ill homeless persons.
Porous Materials from Thermally Activated Kaolinite: Preparation, Characterization and Application

In the present study, porous alumina/silica materials were prepared by selective leaching of silicon/aluminum constituents from thermal-activated kaolinite in inorganic acid or alkali liquor. The correlations between the characteristics of the prepared porous materials and the dissolution properties of activated kaolinite were also investigated. The results show that the specific surface area (SSA) of porous alumina/silica increases with silica/alumina dissolution, but without marked change of the BJH pore size. Furthermore, change in pore volume is more dependent on activation temperature. The porous alumina and silica obtained from alkali leaching of kaolinite activated at 1150 °C for 15 min and acid leaching of kaolinite activated at 850 °C for 15 min are mesoporous, with SSAs, BJH pore sizes and pore volumes of 55.8 m2/g and 280.3 m2/g, 6.06 nm and 3.06 nm, 0.1455 mL/g and 0.1945 mL/g, respectively. According to the adsorption tests, porous alumina has superior adsorption capacities for Cu2+, Pb2+ and Cd2+ compared with porous silica and activated carbon. The maximum capacities of porous alumina for Cu2+, Pb2+ and Cd2+ are 134 mg/g, 183 mg/g and 195 mg/g, respectively, at 30 °C.
Body mass and glucocorticoid response in asthma.

RATIONALE Obesity may alter glucocorticoid response in asthma. OBJECTIVES To evaluate the relationship between body mass index (BMI, kg/m(2)) and glucocorticoid response in subjects with and without asthma. METHODS Nonsmoking adult subjects underwent characterization of lung function, BMI, and spirometric response to prednisone. Dexamethasone (DEX, 10(-6) M)-induced mitogen-activated protein kinase phosphatase-1 (MKP-1) and baseline tumor necrosis factor (TNF)-alpha expression were evaluated by polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage cells. The relationship between BMI and expression of MKP-1 and TNF-alpha was analyzed. MEASUREMENTS AND MAIN RESULTS A total of 45 nonsmoking adults, 33 with asthma (mean [SD] FEV(1)% of 70.7 [9.8]%) and 12 without asthma were enrolled. DEX-induced PBMC MKP-1 expression was reduced in overweight/obese versus lean patients with asthma, with mean (+/- SEM) fold-induction of 3.11 (+/-0.46) versus 5.27 (+/-0.66), respectively (P = 0.01). In patients with asthma, regression analysis revealed a -0.16 (+/-0.08)-fold decrease in DEX-induced MKP-1 per unit BMI increase (P = 0.04). PBMC TNF-alpha expression increased as BMI increased in subjects with asthma, with a 0.27 unit increase in log (TNF-alpha [ng/ml]) per unit BMI increase (P = 0.01). The ratio of PBMC log (TNF-alpha):DEX-induced MKP-1 also increased as BMI increased in patients with asthma (+0.09 +/- 0.02; P = 0.004). In bronchoalveolar lavage cells, DEX-induced MKP-1 expression was also reduced in overweight/obese versus lean patients with asthma (1.36 +/- 0.09-fold vs. 1.76 +/- 0.15-fold induction; P = 0.05). Similar findings were not observed in control subjects without asthma. CONCLUSIONS Elevated BMI is associated with blunted in vitro response to dexamethasone in overweight and obese patients with asthma.