Miracle-dz/UniFAR-FTUs huggingface dataset:
The Drosophila Tis11 Protein and Its Effects on mRNA Expression in Flies*

Background: Insects generally express a single tristetraprolin family member, zinc finger proteins that promote mRNA decay. Results: The Drosophila protein, Tis11, can promote mRNA decay in cells, and its deficiency in flies results in accumulation of certain mRNAs. Conclusion: Tis11 deficiency in Drosophila results in increases of potential target transcripts. Significance: Tis11 can affect post-transcriptional gene expression in adult flies by regulating mRNA decay. Members of the mammalian tristetraprolin family of CCCH tandem zinc finger proteins can bind to certain AU-rich elements (AREs) in mRNAs, leading to their deadenylation and destabilization. Mammals express three or four members of this family, but Drosophila melanogaster and other insects appear to contain a single gene, Tis11. We found that recombinant Drosophila Tis11 protein could bind to ARE-containing RNA oligonucleotides with low nanomolar affinity. Remarkably, co-expression in mammalian cells with “target” RNAs demonstrated that Tis11 could promote destabilization of ARE-containing mRNAs and that this was partially dependent on a conserved C-terminal sequence resembling the mammalian NOT1 binding domain. Drosophila Tis11 promoted both deadenylation and decay of a target transcript in this heterologous cell system. We used chromosome deletion/duplication and P element insertion to produce two types of Tis11 deficiency in adult flies, both of which were viable and fertile. To address the hypothesis that Tis11 deficiency would lead to the abnormal accumulation of potential target transcripts, we analyzed gene expression in adult flies by deep mRNA sequencing. We identified 69 transcripts from 56 genes that were significantly up-regulated more than 1.5-fold in both types of Tis11-deficient flies. Ten of the up-regulated transcripts encoded probable proteases, but many other functional classes of proteins were represented. Many of the up-regulated transcripts contained potential binding sites for tristetraprolin family member proteins that were conserved in other Drosophila species. Tis11 is thus an ARE-binding, mRNA-destabilizing protein that may play a role in post-transcriptional gene expression in Drosophila and other insects.
eQTL Regulating Transcript Levels Associated with Diverse Biological Processes in Tomato1[OPEN]

Genetic mapping and coexpression highlights hot spots regulating transcripts linked to diverse biological processes. Variation in gene expression, in addition to sequence polymorphisms, is known to influence developmental, physiological, and metabolic traits in plants. Genetic mapping populations have facilitated identification of expression quantitative trait loci (eQTL), the genetic determinants of variation in gene expression patterns. We used an introgression population developed from the wild desert-adapted Solanum pennellii and domesticated tomato (Solanum lycopersicum) to identify the genetic basis of transcript level variation. We established the effect of each introgression on the transcriptome and identified approximately 7,200 eQTL regulating the steady-state transcript levels of 5,300 genes. Barnes-Hut t-distributed stochastic neighbor embedding clustering identified 42 modules revealing novel associations between transcript level patterns and biological processes. The results showed a complex genetic architecture of global transcript abundance pattern in tomato. Several genetic hot spots regulating a large number of transcript level patterns relating to diverse biological processes such as plant defense and photosynthesis were identified. Important eQTL regulating transcript level patterns were related to leaf number and complexity as well as hypocotyl length. Genes associated with leaf development showed an inverse correlation with photosynthetic gene expression, but eQTL regulating genes associated with leaf development and photosynthesis were dispersed across the genome. This comprehensive eQTL analysis details the influence of these loci on plant phenotypes and will be a valuable community resource for investigations on the genetic effects of eQTL on phenotypic traits in tomato.
Screening for tuberculosis in jail and clinic follow-up after release.

OBJECTIVES The purpose of this study was to describe tuberculosis (TB) screening and preventive therapy in the San Francisco County Jail and to measure the follow-up rate at the public health department TB clinic. METHODS The records of male inmates screened for 6 months in 1994 were reviewed. Those prescribed isoniazid and released before therapy ended were matched with TB clinic records. Inmates were considered to have followed up if they came to the TB clinic within 1 month of release. RESULTS Of 3352 inmates screened, 553 (16.5%) reported a prior positive skin test, and 330 (26.9%) of 1229 tests placed and read were positive. Of those with positive tests, 151 (45.8%) began isoniazid. Most of the inmates were foreign-born Hispanics (80.8%). Ninety-three (61.6%) inmates were released before completion, after an average of 68.5 days. Three (3.2%) went to the TB clinic within a month. CONCLUSIONS Jail represents an important screening site for TB, but care is not continued after release. Strategies are needed to enhance the continuity of isoniazid preventive care.
Dopamine D3 receptor antisense oligodeoxynucleotide potentiates imipramine-induced dopaminergic behavioural supersensitivity

Chronic antidepressant treatments result in the potentiation of dopaminergic transmission in the mesolimbic dopamine system revealed as an increased motor response to dopamine D2-like agonists. On the basis of the involvement of this system in the control of motivation and reward-related behaviour, which are impaired in depression, it has been suggested that such supersensitivity might play an important role in the mechanism of action of these drugs. Several studies have provided evidence suggesting a role of dopamine D3 receptors in mediating antidepressant-induced increased motor response to dopamine agonists. To test this hypothesis, we studied the effect of the intracerebroventricular infusion of a dopamine D3 receptor antisense oligodeoxynucleotide (10 μg/3 μl, 2–3 daily injections) on the expression of imipramine-induced supersensitivity (20 mg/kg daily intraperitoneal injections for 21 days) to the motor effect of the dopamine D2-like receptor agonist quinpirole (a single 0.3 mg/kg subcutaneous injection 24–48 h after imipramine withdrawal). The results show that a treatment previously shown to reduce the synthesis of dopamine D3 receptors, rather than resulting in an inhibitory effect, potentiated the ability of imipramine to induce dopaminergic motor supersensitivity. The present results suggest that increased dopamine D3 receptor expression following antidepressant treatments is not involved in the mechanism of dopaminergic supersensitivity, and are consistent with evidence supporting an inhibitory role for dopamine D3 receptors in motor activity, both in normal and in sensitized subjects.
Mitochondrial and nuclear DNA phylogeography of Thymallus spp. (grayling) provides evidence of ice‐age mediated environmental perturbations in the world's oldest body of fresh water, Lake Baikal

Theories on the hydrological history of Lake Baikal, the world's oldest and deepest body of freshwater, and its surrounding great rivers, are currently based solely on geological evidence and are conflicting. Baikal is inhabited by numerous zoogeographical enigmas but their high level of endemism has hindered phylogeographic inferences. We provide a biological perspective of the region's palaeo‐hydrological development based on the demographic and genealogical history of the widespread Thymallus spp. (grayling). Phylogenetic reconstruction reveals that old lineages of grayling (pre‐Pleistocene) currently inhabit the Enisey, Lena and Amur River basins. For Lake Baikal however, we conclude that a mid‐Pleistocene colonization (110 000–450 000 years ago) of an unoccupied niche has occurred. Population genetic inferences support an Enisey–Angara river route of colonization into Baikal, corresponding to the cataclysmic palaeo‐hydrological event that led to the formation of the lake's only contemporary outlet, and a subsequent range expansion several thousand kilometres into the uppermost reaches of the Selenga River basin. The evolutionary history of Lake Baikal grayling is congruent with the controversial hypothesis of repeated glaciation. However, considering the extraordinary levels of endemism and proposed Miocene or Oligocene coalescence of other faunal lineages, a less profound but equally consequential cycle of environmental perturbations may have taken place. Bi‐parentally inherited microsatellite DNA loci supported the phylogenetic relationships of Thymallus spp. and the geographical expansion of Baikal grayling strikingly well. A Markov Chain Monte Carlo modelling approach suggested severe contemporary population decline during the last century, possibly reflecting the influence of an uncontrolled fishery on this treasured ecosystem. These complementary pictures of the demographic history of grayling underscore the breadth of historical inquiry that can be entertained through the modelling of sufficient molecular data, and may significantly alter the zoogeographical and limnological perspectives of Baikal's history.
A naturalistic assessment of protriptyline for attention-deficit hyperactivity disorder.

OBJECTIVE To evaluate the potential benefit of the tricyclic antidepressant, protriptyline, in the treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD). METHOD All clinic patients in an outpatient pediatric psychopharmacology unit treated with protriptyline for ADHD were monitored for response to treatment. Thirteen subjects (11 male, 2 female) were treated naturalistically with protriptyline for ADHD and were administered the ADHD Symptom Rating Scale and Clinical Global Impression of Severity (CGI-S) and improvement (CGI-I) at baseline and while taking medication. All patients had failed to respond to at least one previous medication trial, and 46% had psychiatric comorbidity. RESULTS Patients received an average protriptyline dose of 17 mg (range 5 to 30 mg) for 11.5 +/- 6.8 weeks. Of the 11 patients who continued to take protriptyline for at least 4 weeks, there was a modest reduction in the ADHD symptom checklist (p < .004) and the CGI-S (p = .032). However, using a predefined criteria of response, only 45% of patients were considered positive responders. Adverse effects were prominent, with 46% of patients reporting clinically significant problems and 38% of patients discontinuing treatment because of intolerable side effects. CONCLUSION These findings do not support the clinical utility of protriptyline in the routine management of complex cases of ADHD in children and adolescents. However, the usefulness in noncomorbid, medication-naive ADHD individuals remains unclear.
Effects of supplemental protein source on passage of nitrogen to the small intestine, nutritional status of pregnant ewes, and wool follicle development of progeny.

Rambouillet wethers, surgically fitted with ruminal and duodenal cannulas, were used to determine the influence of substituting soybean meal (SBM) with blood meal (BM) in grass hay diets (8.0% CP) on N flow to the small intestine. Treatments were arranged in a 3 x 4 Latin square design and included diets (10.6% CP) supplemented with SBM; 2/3 SBM:1/3 BM; 1/3 SBM:2/3 BM; or BM. Ruminal NH3 N concentration decreased linearly (P = .03) as BM replaced SBM; however, feeding BM did not affect (P > .10) the total N, microbial N, or nonammonia N flows to the small intestine. A second experiment was conducted to determine the influence of substituting SBM with BM on ewe BW and condition score changes, blood metabolite profiles, wool growth, and progeny wool follicle development. Thirty-two pregnant Targhee ewes fed a grass hay diet were allotted randomly to four groups (n = 8) and supplemented with either SBM; 2/3 SBM:1/3 BM; 1/3 SBM:2/3 BM; or BM. Soybean meal, BM, or their combinations provided 22 g of dietary CP daily. Dietary treatments had no influence on ewe BW (P = .40) or body condition score (P = .77) changes, and ewes gained 7.6 kg of BW during the 84-d experiment. Protein source did not influence (P > .10) serum protein, urea N, creatinine, glucose, or nonesterified fatty acid concentrations. Lamb wool follicle density per square millimeter and secondary:primary follicle ratios were 22.4 and 10.8, respectively, and were not different (P > .10) among dietary treatments. Compared with SBM, no advantages were detected for BM supplementation of grass hay diets in these studies.
Dopamine transporter imaging and SPECT in diagnostic work‐up of Parkinson's disease: A decision‐analytic approach

As a diagnostic test for patients with suspected Parkinson's disease (PD), single photon emission computed tomography (SPECT) using [123I]FP‐CIT tracer has better sensitivity but is more expensive than regular clinical examination (CE). Our objective was to evaluate the clinical and economic impacts of different diagnostic strategies involving [123I]FP‐CIT SPECT. We developed a decision tree model to predict adequate treatment‐month equivalents (ATME), costs, and incremental cost–effectiveness ratio (ICER) during a 12‐month time horizon in patients with suspected PD referred to a specialized movement disorder outpatient clinic. In our cost– effectiveness analysis, we adopted the perspective of the German health care system and used data from a German prospective health care utilization study (n = 142) and published diagnostic studies. Compared strategies were CE only (EXAM+), SPECT only (SPECT+), SPECT following negative CE (SINGLE+), and SPECT following positive CE (DOUBLE+). Costs of SPECT amounted to €789 per investigation. Based on our model, expected costs (and ATME) were €946 (52.85 ATME) for EXAM+, €1352 (53.40 ATME) for DOUBLE+, €1731 (32.82 ATME) for SINGLE+, and €2003 (32.96 ATME) for SPECT+; performance of SPECT was induced in 0%, 54%, 56%, and 100% of the patients, respectively. DOUBLE+ was more effective and less expensive than SINGLE+ or SPECT+; thus these two do not offer reasonable choices. The ICER of DOUBLE+ compared to EXAM+ was €733 per ATME gained. In sensitivity analyses, the ICER of DOUBLE+ versus EXAM+ ranged from €63 to €2411 per ATME gained. Whether the diagnostic work‐up of patients referred to a specialized movement disorder clinic with a high prevalence of PD should include [123I]FP‐CIT SPECT depends on patient preferences and the decision maker's willingness to pay for adequate early treatment. SPECT should be used as a confirmatory test before treatment initiation and limited to patients with a positive test result in the clinical examination. These results should be adjusted to the specific setting and individual patient preferences. © 2003 Movement Disorder Society
BHRF1, the Epstein-Barr virus gene with homology to Bc12, is dispensable for B-lymphocyte transformation and virus replication

The Epstein-Barr virus (EBV) BHRF1 open reading frame is abundantly expressed early in the lytic replication cycle. BHRF1 is also transiently expressed in some latently infected cell lines in the absence of expression of other lytic cycle proteins. BHRF1 shares distant, but significant, colinear primary amino acid sequence homology to Bc12, a cellular gene strongly implicated in the evolution of follicular lymphoma. The experiments reported here used a molecular genetic approach to examine the role of BHRF1 in EBV infection. Isogenic EBV recombinants having either wild-type BHRF1 or a null mutation due to a translational stop signal in place of the 24th BHRF1 codon were used to infect primary B lymphocytes. The BHRF1 mutant recombinants did not differ from the wild type in their ability to infect and transform the growth of primary B lymphocytes, to replicate in the resultant lymphoblastoid cell lines, or to initiate a second round of primary cell transformation. Deletion of the entire BHRF1 open reading frame did not destroy the ability of the mutant virus to maintain cell growth transformation. The significance of these findings with regard to the role of BHRF1 in EBV infection is discussed.
Antigenic structure of the influenza B virus hemagglutinin: nucleotide sequence analysis of antigenic variants selected with monoclonal antibodies

We report here the complete nucleotide sequence of the hemagglutinin (HA) gene of influenza B virus B/Oregon/5/80 and, through comparative sequence analysis, identify amino acid substitutions in the HA1 polypeptide responsible for the antigenic alterations in laboratory-selected antigenic variants of this virus. The complete nucleotide sequence of the B/Oregon/5/80 HA gene was established by a combination of chemical sequencing of a full-length cDNA clone and dideoxy sequencing of the virion RNA. The nucleotide sequence is very similar to previously reported influenza B virus HA gene sequences and differs at only nine nucleotide positions from the B/Singapore/222/79 HA gene (Verhoeyen et al., Nucleic Acids Res. 11:4703-4712, 1983). The nucleotide sequences of the HA1 portions of the HA genes of 18 laboratory-selected antigenic variants were determined by the dideoxy method. Comparison of the deduced amino acid sequences of the parental and variant HA1 polypeptides revealed 16 different amino acid substitutions at nine positions. All amino acid substitutions resulted from single-point mutations, and no double mutants were detected, demonstrating that as in the influenza A viruses, single amino acid substitutions are sufficient to alter the antigenicity of the HA molecule. Many of the amino acid substitutions in the variants occurred at positions also observed to change in natural drift strains. The substitutions appear to identify at least two immunodominant regions which correspond to proposed antigenic sites A and B on the influenza A virus H3 HA.
Direct detection of Mycobacterium tuberculosis complex in respiratory specimens by Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test and Roche Amplicor Mycobacterium Tuberculosis Test

Two hundred and fifty-six sputum, bronchoalveolar lavage, and bronchial and tracheal aspirate specimens from 243 patients were tested for the presence of Mycobacterium tuberculosis complex by auramine fluorochrome staining, rRNA target amplification (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test [AMTD]), and PCR (Roche Amplicor Mycobacterium Tuberculosis Test [Amplicor PCR]. The results were compared with those of conventional Löwenstein-Jensen tube culture and BACTEC radiometric liquid culture. A total of 26 specimens from 18 patients were culture positive for M. tuberculosis. In addition, seven specimens were positive by staining and by culture for other Mycobacterium species but negative by nucleic acid amplification methods and were not included in the comparison. When compared with that for culture, the sensitivities of the techniques were as follows: for staining, 80.8%; for Gen-Probe AMTD, 84.6%; and for Roche Amplicor PCR, 84.6%. The specificities were 99.1, 98.7, and 99.1%, respectively. After resolution of discrepant results by review of the patients' clinical data, 29 specimens from 21 patients were considered positive, and the overall sensitivities, specificities, and positive and negative predictive values were 89.7, 100, 100, and 98.7% for culture; 75.9, 99.5, 95.7, and 96.9% for staining; 86.2, 100, 100, and 98.2% for Gen-Probe AMTD; and 82.8, 100, 100, and 97.9% for Roche Amplicor PCR, respectively. It is concluded that both nucleic acid amplification methods are rapid, sensitive, and specific methods for the detection of M. tuberculosis in respiratory specimens.
Mammalian cells loaded with platinum-containing molecules are sensitized to fast atomic ions

Purpose: This work investigates whether a synergy in cell death induction exists in combining atomic ions irradiation and addition of platinum salts. Such a synergy could be of interest in view of new cancer therapy protocol based on atomic ions – hadrontherapy – with the addition of radiosensitizing agents containing high-Z atoms. The experiment consists in irradiating by fast ions cultured cells previously exposed to dichloroterpyridine Platinum (PtTC) and analyzing cell survival by a colony-forming assay. Materials and methods: Chinese Hamster Ovary (CHO) cells were incubated for six hours in medium containing 350 μM PtTC, and then irradiated by fast ions C6+ and He2+, with Linear Energy Transfer (LET) within range 2–70 keV/μm. In some experiments, dimethyl sulfoxide (DMSO) was added to investigate the role of free radicals. The intracellular localization of platinum was determined by Nano Secondary Ion Mass Spectroscopy (Nano-SIMS). Results: For all LET examined, cell death rate is largely enhanced when irradiating in presence of PtTC. At fixed irradiation dose, cell death rate increases with increasing LET, while the platinum relative effect is larger at low LET. Conclusion: This finding suggests that hadrontherapy or protontherapy therapeutic index could be improved by combining irradiation procedure with concomitant chemotherapy protocols using platinum salts.
Virologic and Clinical Outcomes of Hepatitis B Virus Infection in HIV‐HBV Coinfected Transplant Recipients

Liver transplantation (LT) is the treatment of choice for end‐stage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV‐hepatitis B virus (HBV) coinfected patients transplanted between 2001–2007; outcomes including survival and HBV clinical recurrence were determined. Twenty‐two coinfected patients underwent LT; 45% had detectable HBV DNA pre‐LT and 72% were receiving anti‐HBV drugs with efficacy against lamivudine‐resistant HBV. Post‐LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow‐up 3.5 years. Low‐level HBV viremia (median 108 IU/mL, range 9–789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow‐up of 4.0 years, patient and graft survival were similar: 100% versus 85% in HBV mono‐ versus coinfected patients (p = 0.08, log rank test). LT is effective for HIV‐HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low‐level HBV DNA is detectable in ∼50% of recipients.