Miracle-dz/UniFAR-FTUs huggingface dataset:
No evidence for adaptation to local rhizobial mutualists in the legume Medicago lupulina

Local adaptation is a common but not ubiquitous feature of species interactions, and understanding the circumstances under which it evolves illuminates the factors that influence adaptive population divergence. Antagonistic species interactions dominate the local adaptation literature relative to mutualistic ones, preventing an overall assessment of adaptation within interspecific interactions. Here, we tested whether the legume Medicago lupulina is adapted to the locally abundant species of mutualistic nitrogen-fixing bacteria (“rhizobia”), which vary in frequency across its eastern North American range. We reciprocally inoculated northern and southern M. lupulina genotypes with the northern (Ensifer medicae) or southern bacterium (E. meliloti) in a greenhouse experiment. Neither northern nor southern plants produced more seed flowered earlier, or were more likely to flower when inoculated with their local rhizobium species, although plants produced more root nodules (the structures that house the bacteria) wit their local rhizobia. We used a pre-existing dataset to perform a genome scan for loci that showed elevated differentiation between field-collected plants that hosted different bacteria. None of the loci we identified belonged to the well-characterized suite of legume-rhizobia symbiosis genes, suggesting that the rhizobia do not drive genetic divergence between M. lupulina populations. Our results demonstrate that symbiont local adaptation is weak in this mutualism despite large-scale geographic variation in the identity of the interacting species.
A Probabilistic Model to Investigate the Properties of Prognostic Tools for Falls

Summary Background: Falls are a prevalent and burdensome problem in the elderly. Tools for the assessment of fall risk are fundamental for fall prevention. Clinical studies for the development and evaluation of prognostic tools for falls show high heterogeneity in the settings and in the reported results. Newly developed tools are susceptible to over- optimism. Objectives: This study proposes a probabilistic model to address critical issues about fall prediction through the analysis of the properties of an ideal prognostic tool for falls. Methods: The model assumes that falls occur within a population according to the Greenwood and Yule scheme for accident-proneness. Parameters for the fall rate distribution are estimated from counts of falls of four different epidemiological studies. Results: We obtained analytic formulas and quantitative estimates for the predictive and discriminative properties of the ideal prognostic tool. The area under the receiver operating characteristic curve (AUC) ranges between about 0.80 and 0.89 when prediction on any fall is made within a follow-up of one year. Predicting on multiple falls results in higher AUC. Conclusions: The discriminative ability of current validated prognostic tools for falls is sensibly lower than what the proposed ideal perfect tool achieves. A sensitivity analysis of the predictive and discriminative properties of the tool with respect to study settings and fall rate distribution identifies major factors that can account for the high heterogeneity of results observed in the literature.
Fluconazole Susceptibility Testing of Cryptococcus neoformans: Comparison of Two Broth Microdilution Methods and Clinical Correlates among Isolates from Ugandan AIDS Patients

ABSTRACT We compared the yeast nitrogen base (YNB) broth microdilution method with the National Committee for Clinical Laboratory Standards (NCCLS) M27-A microdilution reference method for measuring the in vitro susceptibility of Cryptococcus neoformans isolates to fluconazole. A total of 149 isolates of C. neoformans var.neoformans from Ugandan AIDS patients was tested by both methods. An overall agreement of 88% between the two microdilution methods was observed. All isolates grew well in both RPMI 1640 and YNB media, and MICs could be read after 48 h of incubation by both methods. The range of fluconazole MICs obtained with the YNB method was broader than that obtained with the NCCLS method. The extended range of MICs provided by the YNB method may be of clinical value, as it appears that the clinical outcome may be better among patients infected with strains inhibited by lower concentrations of fluconazole as determined by the YNB method. The YNB method appears to be a viable option for testing C. neoformans against fluconazole.
Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses.

BACKGROUND Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. OBJECTIVE The aim of this study was to compare hair follicle stages in PPID-affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID-affected horses after 6 months of treatment with pergolide mesylate with those of control horses. ANIMALS Eight PPID-affected horses and four normal, age-matched, control horses. METHODS Skin biopsies were collected from the neck and rump of PPID-affected and control horses. A diagnosis of PPID was established based on hair coat changes and supportive overnight dexamethasone suppression test results. Skin biopsies were repeated after 6 months of treatment with pergolide. The number of hair follicles in anagen (A) or telogen (T) was counted for each skin biopsy using transverse sections. RESULTS Pretreatment biopsies had a greater percentage of A follicles (neck 96%, rump 95%) and a lower percentage of T follicles (neck 4%, rump 5%) in PPID-affected horses than in control horses (A, neck 15%, rump 25%; and T, neck 85%, rump 75%). After treatment with pergolide, all PPID-affected horses had improved shedding, and the percentages of A follicles (neck 69%, rump 70%) and T follicles (neck 31%, rump 30%) were not different from untreated control horses (A, neck 68%, rump 82%; and T, neck 32%, rump 18%). CONCLUSIONS These findings document that excessive hair growth (hypertrichosis) in PPID-affected horses is due to persistence of hair follicles in A. Furthermore, treatment with pergolide improved shedding and reduced the percentage of A follicles in PPID-affected horses.
Composition of Toluene-Degrading Microbial Communities from Soil at Different Concentrations of Toluene

ABSTRACT Toluene-degrading bacteria were isolated from hydrocarbon-contaminated soil by incubating liquid enrichment cultures and agar plate cultures in desiccators in which the vapor pressure of toluene was controlled by dilution with vacuum pump oil. Incubation in desiccators equilibrated with either 100, 10, or 1% (wt/wt) toluene in vacuum pump oil and testing for genomic cross-hybridization resulted in four genomically distinct strains (standards) capable of growth on toluene (strains Cstd1, Cstd2, Cstd5, and Cstd7). The optimal toluene concentrations for growth of these standards on plating media differed considerably. Cstd1 grew best in an atmosphere equilibrated with 0.1% (wt/wt) toluene, but Cstd5 failed to grow in this atmosphere. Conversely, Cstd5 grew well in the presence of 10% (wt/wt) toluene, which inhibited growth of Cstd1. 16S ribosomal DNA sequencing and cross-hybridization analysis indicated that both Cstd1 and Cstd5 are members of the genus Pseudomonas. An analysis of the microbial communities in soil samples that were incubated with 10% (wt/wt) toluene with reverse sample genome probing indicated thatPseudomonas strain Cstd5 was the dominant community member. However, incubation of soil samples with 0.1% (wt/wt) toluene resulted in a community that was dominated by Pseudomonas strain Q7, a toluene degrader that has been described previously (Y. Shen, L. G. Stehmeier, and G. Voordouw, Appl. Environ. Microbiol. 64:637–645, 1998). Q7 was not able to grow by itself in an atmosphere equilibrated with 0.1% (wt/wt) toluene but grew efficiently in coculture with Cstd1, suggesting that toluene or metabolic derivatives of toluene were transferred from Cstd1 to Q7.
Parental Consanguinity and the Risk of Primary Immunodeficiency Disorders: Report from the Kuwait National Primary Immunodeficiency Disorders Registry

Background: It is proposed that consanguineous marriages increase the risk of primary immunodeficiency disorders (PID). The aim of this study is to review the frequency and pattern of parental consanguinity among PID patients and to determine its effects on the distribution of different PID, the patients’ performance status and the risk of death. Method: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. The coefficient of inbreeding was determined for each patient and the patients’ overall performance status was assessed using the Lansky Play Performance Scale and the Karnofsky Performance Scale. Results: A total of 128 patients with PID from 99 families are reported. A family history suggestive of PID and parental consanguinity was reported in 44 and 75% of the patients respectively, while the mean coefficient of inbreeding was 0.044067. There were statistically significant associations between both a family history of PID and parental consanguinity and PID category, the risk of death and the patients’ overall performance status. Evidence of autosomal recessive transmission of disease was present in 44% of the patients. Conclusions: Parental consanguinity is a risk factor for the development of PID. There is a need to increase the public awareness of the health consequences of consanguineous marriages.
The behavioral phenotype of Mowat–Wilson syndrome

Mowat–Wilson syndrome (MWS) is caused by a heterozygous mutation or deletion of the ZEB2 gene. It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia, and Hirschsprung disease. The current study investigated the behavioral phenotype of MWS. Parents and carers of 61 individuals with MWS completed the Developmental Behavior Checklist. Data were compared with those for individuals selected from an epidemiological sample of people with ID from other causes. The behaviors associated with MWS included a high rate of oral behaviors, an increased rate of repetitive behaviors, and an under‐reaction to pain. Other aspects of the MWS behavioral phenotype are suggestive of a happy affect and sociable demeanor. Despite this, those with MWS displayed similarly high levels of behavioral problems as those with intellectual disabilities from other causes, with over 30% showing clinically significant levels of behavioral or emotional disturbance. These findings have the potential to expand our knowledge of the role of the ZEB2 gene during neurodevelopment. Furthermore, they are a foundation for informing interventions and management options to enhance the independence and quality of life for persons with MWS. © 2012 Wiley Periodicals, Inc.
Antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugated with polyglutamic acid and its derivative.

Four types of 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates with poly-L-glutamic acid (PLGA) or poly-N5-(2-hydroxyethyl)-L-glutamine (PHEG) were prepared in an attempt to enhance the efficacy of the drug in simple dosage schedules. The conjugates were made by linking ara-C to the carboxyl groups of PLGA directly at N-4 of ara-C (ara-C:PLGA) or indirectly through the 2-aminoethylphosphoryl or 6-aminohexylphosphoryl side chain which had been introduced to C-5' of ara-C, 1-[5'-(2-aminoethylphosphoryl)-beta-D-arabinofuranosyl]cytosine: PLGA [araCMP(C2):PLGA and 1-[5'-(6-aminohexylphosphoryl)-beta-D-arabinofuranosyl]cytosine:++ +PLGA, respectively, or made by converting the remaining carboxyl groups in the PLGA conjugates to the 2-hydroxyethylamide groups [ara-C:PHEG, ara-CMP(C2):PHEG, 1-[5'-(6-aminohexylphosphoryl)-beta-D-arabinofuranosyl]cytosine:++ +PHEG]. Studies in vitro showed that the conjugates had decreased cytotoxicity against L1210 cells when compared with that of ara-C. Studies in vivo showed that all of the conjugates, except ara-CMP(C2):PLGA, had a greater antitumor activity than did ara-C in L1210 tumor-bearing BALB/c X DBA/2 F, (hereafter called CD2F1) mice (inoculum, 1 X 10(5) cells i.p. on Day 0) which were treated by a single i.p. injection of either the conjugates or the control ara-C on Day 1. The largest antitumor activity [increased life span (ILS) 170%] was observed with a dosage of 50 mg (equivalent ara-C per kg) of ara-C:PHEG. When CD2F1 mice which had been inoculated i.p. with 1 X 10(5) L1210 cells were treated with an i.p. injection of 12.5 or 25 mg (equivalent ara-C per kg) of ara-C:PHEG daily for 5 days starting from Day 1, 2 of 5 mice survived more than 42 days, and the ILS of the remaining mice was 153 and 184%. The injections of 3.2 mg (equivalent ara-C per kg) of ara-C:PHEG showed a moderate antitumor activity with an ILS of 113% which was similar to the ILS (119%) found when unconjugated ara-C (400 mg/kg) was used to treat tumor-bearing mice. In in vitro release experiments, ara-C was released slowly from ara-C:PLGA at pH 7.4, and ara-CMP(C2):PLGA was chemically stable but cleaved by phosphodiesterase, acid phosphatase, and alkaline phosphatase to give mainly 1-beta-D-arabinofuranosylcytosine 5'-monophosphate.
Derivatives and Risk: The Case of Thrifts

The authors examine the relationship between derivatives use and the interest-rate risk of US savings associations during the period 1993-1997. Advantages of the use of thrift data, as opposed to commercial bank data, include markedly superior detail, a homogeneous industry, the industry's inherent interest-rate risk, interest-rate sensitivitymeasures derived from a single model (the OTS Net Portfolio Value model), market values, and the lack of distortions in the data owing to the presence of dealers. It is found that, after controlling for firm characteristics, thrifts use derivatives to reduce interest-rate risk and vulnerability to capital compliance problems. Additionally, after controlling for interest-rate risk and credit risk, derivatives users have higher net interest margins. The lack of usage by smaller institutions suggests that a significant segment of the industry is limited in its ability to manage interest-rate risk efficiently.
Differential and complementary roles of medial and lateral septum in the orchestration of limbic oscillations and signal integration

Anatomical differences between the medial and lateral septum have associated these nuclei with dissimilar functional roles and behaviours. While the medial septum has been implicated, predominantly, in theta rhythm generation along the septo‐hippocampal axis, the lateral septum has mainly been investigated in the context of septo‐hypothalamic dialogue. Recent advances suggest that medial and lateral septum are more closely functionally related than previously appreciated. Here, we explore the hypothesis that the medial septum mediates ascending septo‐hippocampal theta propagation, while the lateral septum processes a descending hippocampo‐septal and septo‐hypothalamic reinforcement signal that mediates navigation during motivated behaviour. The generation and propagation of theta rhythm are critical for the initiation of exploratory behaviour. Indeed, theta signal processing of medial and lateral septum nuclei may well be involved in the integration of spatial, rewarding and locomotor signals across different brain networks. We review here the structural features, anatomical connectivity and functional properties of the medial and lateral septum. We discuss the heterogeneous anatomy of the lateral septum, which is composed of diverse subregions with distinct ascending and descending projections, and we relate the physiological characteristics of septal nuclei to their functional relationships with the hippocampal formation, the hypothalamus and the brainstem reticular formation during motivated spatial navigation.
Psychological implications of infertility in women with polycystic ovary syndrome.

BACKGROUND In polycystic ovary syndrome (PCOS), one of the main features is chronic anovulation associated with lower pregnancy rates. Little is known regarding the psychological aspects associated with infertility in these patients. Therefore, we examined the influence of an unfulfilled wish to conceive on various aspects of psychological functioning in PCOS women. METHODS Standardized questionnaires assessing quality-of-life (36-item short-form health survey, SF-36), depressiveness (Beck Depression Inventory), emotional distress (Symptom Check List 90, SCL-90-R), sexual satisfaction and self-worth (visual analogue scales), and a questionnaire on the desire for a child (FKW) were administered at the outpatient endocrine clinic to consecutive PCOS patients. RESULTS Questionnaires from 115 PCOS patients were analysed. The majority (76.1%) worried about remaining childless in the future, and 51.3% reported a current wish to conceive. 23.9% of patients had scores indicating mild to moderate depression, and 25.2% had scores indicating clinically relevant depression. Furthermore, all quality-of-life scores were significantly lower compared with normative data (P < 0.001). Unexpectedly, comparisons of patients with a current unfulfilled desire to conceive to those with no present wish for a child revealed no discernable impact on depressive symptoms, quality-of-life or emotional distress. Reduced sexual satisfaction and self-worth were largely determined by partnership status and not infertility. However for PCOS patients who wished to conceive, the wish for a child was a significantly greater priority when compared with normative data from infertile patients. CONCLUSIONS PCOS represents a major risk factor for psychosocial and emotional problems, but at least in this sample of PCOS patients, infertility does not appear to constitute a primary determinant of psychological problems.
Meiotic recombination between dispersed repeated genes is associated with heteroduplex formation

In Saccharomyces cerevisiae, recombination events occurring between allelic genes located on homologous chromosomes are often associated with heteroduplex formation. We found that recombination events between repeated genes on nonhomologous chromosomes (ectopic events) are also associated with the formation of heteroduplexes, indicating that classical and ectopic recombination events involve similar mechanisms.
Repression of nuclear CELF activity can rescue CELF-regulated alternative splicing defects in skeletal muscle models of myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is caused by the expansion of CUG repeats in the 3’ UTR of DMPK transcripts. DM1 pathogenesis has been attributed in part to alternative splicing dysregulation via elevation of CUG-BP, Elav-like family member 1 (CELF1). Several therapeutic approaches have been tested in cells and mice, but no previous studies had specifically targeted CELF1. Here, we show that repressing CELF activity rescues CELF-dependent alternative splicing in cell culture and transgenic mouse models of DM1. CELF-independent splicing, however, remained dysregulated. These data highlight both the potential and limitations of targeting CELF1 for the treatment of DM1.
Is mother-child transmission a possible vehicle for xylitol prophylaxis in acute otitis media?

Abstract Objective: Xylitol can be a prophylaxis for acute otitis media (AOM), especially when administered via chewing gum, but that vehicle has limitations for children. This review sought evidence for links of mother-child transmission of bacteria and as a vehicle for xylitol as a prophylaxis for dental caries and its translation to AOM in infants and young children. Design: Qualitative systematic review. Method: Combining output from 43 search strings used earlier and submitting 20 new strings to PubMed resulted in 14 studies (six were excluded; eight were included). Included studies had to be published in English-language, peer-reviewed journals; involve mothers using xylitol; and assess bacteria or caries in their children. Evaluation forms were completed for search, retrieval, and quality assessment of included studies. Results: The studies showed that mothers’ chewing xylitol gum was a prophylaxis against bacteria and caries in their children. A mother-child transmission model was presented as a possible vehicle for use in comprehensive prevention programs for AOM. Conclusions: Potential for xylitol use to prevent AOM warrants further study. A mother-child model may apply to AOM for transmission of bacteria and as a prophylaxis, but alternative vehicles like nasal sprays should be investigated for ease of use and effectiveness. Sumario Objetivo: El Xylitol puede ser un profiláctico para la otitis media aguda (AOM), especialmente cuando se administra en forma de goma de mascar, pero ese vehiculo tiene sus limitaciones en los niños. Esta revisión buscó evidencias sobre la conexión de la transmisión de la bacteria entre madre e hijo y el Xylitol como vehículo de profilaxis para la caries dental y su conversión a AOM en bebés y niños. Diseño: Revisión sistemática cuantitativa. Metodo: Se combinaron los resultados de 43 líneas de búsqueda utilizadas anteriormente con 20 nuevas líneas de búsqueda a PubMed; se obtuvieron 14 estudios (se excluyeron seis y se incluyeron ocho). Los estudios incluidos tenían que estar publicados en revistas en inglés, con revisión editorial; que incluyeran a madres utilizando Xylitol; y una evaluación de bacterias o caries en sus niños. Resultados: Los estudios demostraron que las madres que masticaban Xylitol eran un profiláctico contra bacterias y caries en sus niños. Se presenta un modelo de transmisión madre-hijo como posible vehículo para ser utilizado en los programas de prevención integral de la AOM. Conclusiones: El potencial del Xylitol en la prevención de la AOM requiere mayor estudio. Es posible que se pueda aplicar un modelo de transmisión de bacterias entre madre e hijo en la AOM y como profiláctico; pero un vehículo alternativo como el spray nasal debe ser investigado para facilitar su uso y efectividad.