Miracle-dz/UniFAR-FTUs huggingface dataset:
Sympatric speciation of spiny mice, Acomys, unfolded transcriptomically at Evolution Canyon, Israel

Significance Sympatric speciation (SS) has always been controversial since it was proposed by Darwin. Recently, we showed SS empirically in Spalax by amplified fragment-length polymorphism (AFLP), mitochondrial, and nuclear genomes. Similarly, SS in spiny mice, Acomys, from Evolution Canyon I (EC I), was earlier proposed by mtDNA and AFLP. Here, we show that full transcriptome data substantiates SS under sharp microclimatic and ecological divergence with gene flow, displaying extensive adaptive complexes to slope-specific stresses coupled with habitat choice and signals of reproductive isolation. Remarkably, strong natural selection across a sharply divergent ecological microsite overrules gene flow and advances SS, which is common at EC I. Because microsite ecological, geological, edaphic, and climatic divergences are widespread in nature, we conclude that SS might be a common mode of speciation. Spiny mice, Acomys cahirinus, colonized Israel 30,000 y ago from dry tropical Africa and inhabited rocky habitats across Israel. Earlier, we had shown by mtDNA that A. cahirinus incipiently sympatrically speciates at Evolution Canyon I (EC I) in Mount Carmel, Israel because of microclimatic interslope divergence. The EC I microsite consists of a dry and hot savannoid “African” slope (AS) and an abutting humid and cool-forested “European” slope (ES). Here, we substantiate incipient SS in A. cahirinus at EC I based on the entire transcriptome, showing that multiple slope-specific adaptive complexes across the transcriptome result in two divergent clusters. Tajima’s D distribution of the abutting Acomys interslope populations shows that the ES population is under stronger positive selection, whereas the AS population is under balancing selection, harboring higher genetic polymorphisms. Considerable sites of the two populations were differentiated with a coefficient of FST = 0.25–0.75. Remarkably, 24 and 37 putatively adaptively selected genes were detected in the AS and ES populations, respectively. The AS genes involved DNA repair, growth arrest, neural cell differentiation, and heat-shock proteins adapting to the local AS stresses of high solar radiation, drought, and high temperature. In contrast, the ES genes involved high ATP associated with energetics stress. The sharp ecological interslope divergence led to strong slope-specific selection overruling the interslope gene flow. Earlier tests suggested slope-specific mate choice. Habitat interslope-adaptive selection across the transcriptome and mate choice substantiate sympatric speciation (SS), suggesting its prevalence at EC I and commonality in nature.
Exploring allelic imbalance within paraffin-embedded tumor biopsies using pyrosequencing technology

Abstract Background: The comparison of molecular genetic changes in healthy and pathological tissues has historically led to the identification of oncogenes and tumor suppressor genes. It is very common that studies investigating loss of heterozygosity are carried out retrospectively on paraffin-embedded samples. Methods: In this study, we evaluated the power of pyrosequencing for determining the loss of heterozygotic regions. The present method uses the fact that pyrosequencing is an accurate, sensitive and reproducible technique. The method is also simple to perform, with results available in 96-well format, making the assays amenable to automation. Thus, we analyzed nine single nucleotide polymorphisms along 1Mb between the EMSY and PAK1 genes on 11q13, a region frequently rearranged in different tumors and cell lines. We assessed the study using samples from breast cancer and thyroid cancer biopsies. Results and conclusions: We conclude that this technique is capable of detecting variations of >10% in allele loss. However, strong allele imbalances were detected, depending on the origin of the sample. Seven out of the nine markers used exhibited differential allele amplification, depending on the DNA quality (p<0.01). Clin Chem Lab Med 2006;44:1076–81.
Direct CD28 Costimulation Is Required for CD8+ T Cell-Mediated Resistance to an Acute Viral Disease in a Natural Host1

Previous studies have suggested that, differing from model Ags, viruses that replicate extensively in the host still induce normal CD8+ T cell responses in the absence of CD28 costimulation. Because these studies were performed with viruses that do not normally cause acute disease, an important remaining question is whether CD28 costimulation is required for CD8+ T cell-mediated resistance to widely replicating but pathogenic viruses. To address this question, we studied the role of CD28 costimulation in CD8+ T cell-mediated resistance to mousepox, a disease of the mouse caused by the natural mouse pathogen, the ectromelia virus (ECTV). C57BL/6 (B6) mice are naturally resistant to mousepox, partly due to a fast and strong CD8+ T cell response. We found that B6 mice deficient in CD28 (CD28 knockout (KO)) are highly susceptible to lethal mousepox during the early stages of ECTV infection but can be protected by immunization with the antigenically related vaccinia virus (VACV) or by adoptive transfer of CD28 KO anti-VACV memory CD8+ cells. Of interest, a thorough comparison of the CD8+ T cell responses to ECTV and VACV suggests that the main reason for the susceptibility of CD28 KO mice to mousepox is a reduced response at the early stages of infection. Thus, while in the absence of CD28 costimulation the end point strength of the T cell responses to nonpathogenic viruses may appear normal, CD28 costimulation increases the speed of the T cell response and is essential for resistance to a life-threatening acute viral disease.
MicroRNA gene polymorphisms and the risk of colorectal cancer

The present study was carried out to demonstrate the epidemiological value of microRNA (miRNA) in colorectal cancer (CRC) by investigating the association between miRNA gene polymorphisms and the susceptibility to CRC. Multiple meta-analyses of reported data were conducted, and odds ratio values and 95% confidence intervals were used to assess these associations. Stata 11.0 software was used to analyze the data and the modified Jadad quality score was employed to evaluate the quality of the retrieved studies. We retrieved 38 studies on the association between miRNA polymorphisms and risk of CRC, however only 15 met the requirements of the inclusion criteria. In conclusion, we identified a variety of miRNAs (miRNA-let-7, miR-34b/c, miR-146a, miR-603 and miR-149) gene polymorphisms that are associated with susceptibility to CRC. However, some miRNAs (miR-192a, miR-608 and miR-27a) are associated with CRC, but not susceptibility to CRC. The results have limitations given the relatively low number of studies available. Therefore, it is necessary to collect data from large sample-size studies to further validate the results.
Time Course and Cellular Distribution of Hsp27 and Hsp72 Stress Protein Expression in a Quantitative Gerbil Model of Ischemic Injury and Tolerance: Thresholds for Hsp72 Induction and Hilar Lesioning in the Context of Ischemic Preconditioning

The distribution and time course of expression of the heat shock/stress proteins, hsp27 and hsp72, were evaluated in a highly controlled gerbil model of ischemic injury and tolerance induction, in which the duration of ischemic depolarization in each hippocampus provides a precise quantitative index of insult severity. Gerbils were subjected to brief priming insults (2- to 3.5-minute depolarization) that produce optimal preconditioning, to severe test insults (6- to 8.5-minute depolarization) that produce complete CA1 neuron loss in naive animals, or to combined insults administered 1 week apart, after which almost complete tolerance to CA1 neuron injury is observed. Immunoreactivities of hsp27, hsp72, glial fibrillary acidic protein and microtubule-associated protein 2 (MAP2) were evaluated in animals perfused at defined intervals after the final insult in each treatment group, using a variation of established antigen-retrieval procedures that significantly improves detection of many proteins in vibratome brain sections. Hsp72 was detected in CA1 neurons of some hippocampi 2 to 4 days after preconditioning, but this was only seen after the longest priming depolarizations, whereas shorter insults that still induced optimal tolerance failed to induce hsp72. Hsp72 was induced after test insults in preconditioned hippocampi, but at a higher depolarization threshold than observed for naive animals. An astrocytic localization of hsp27 was observed in regions of neuron injury, as indicated by reduced MAP2 immunoreactivity, and was primarily restricted to dentate hilus after preconditioning insults. These results establish that limited hilar lesions are characteristic of optimal preconditioning, whereas prior neuronal expression of either hsp72 or hsp27 is not required for ischemic tolerance.
The Metabotropic Glutamate Receptor mGluR4, but Not mGluR1α, Is Palmitoylated when Expressed in BHK Cells

Abstract: Several G protein‐coupled receptors have been shown to be palmitoylated, and for some of these receptors the covalent attachment of palmitate has been implicated in the regulation of receptor‐G protein coupling. The metabotropic glutamate receptor (mGluR) family forms a distinct group of G protein‐coupled receptors, and the possibility that these may also be palmitoylated has been examined. Clonal baby hamster kidney (BHK) cells permanently transfected with the mGluR4 and mGluR1α subtypes were labelled with [3H]palmitic acid. The cells were lysed, the receptors were immuno‐precipitated with specific antipeptide antibodies, and the immunoprecipitates were analysed by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis and autoradiography. The palmitoylated, endogenously expressed G protein α‐subunit αq could be immunoprecipitated from [3H]palmitate‐labelled BHK cells expressing mGluR1α using a specific antipeptide antibody, but in the same cell lysates no detectable [3H]palmitate‐labelled mGluR1α was found. This suggests that this mGluR subtype, associated with stimulation of phospholipase C, is not palmitoylated. In contrast, mGluR4, which is coupled to inhibition of adenylyl cyclase, was found to be labelled with [3H]palmitic acid, and the palmitate was quantitatively removed by treatment with 1 M hydroxylamine, suggesting attachment of the palmitate through a thioester bond. Stimulation with maximal doses of the neurotransmitter glutamate for 1, 5, or 10 min appeared to have no effect on the level of receptor palmitoylation.
Guanabara’s bay fortifications: memory as environmental education for military personnel

In its five centuries of history, the process of building Brazil as a nation has left an expressive patrimony where dozens of fortifications are found throughout the Brazilian territory, particularly. Aiming at preserving these architectural ensembles, legal instruments have been multiplying from the organs of public power that are pointing directly towards the preservation of historical-cultural and environmental patrimony. Goal. Using memory as an exercise to build an environmental knowledge (environmental education) by military students who served in the Fort of Leme. Methodology. Effective semi-structured interviews were to lift the process of creating the APA-LEME and revitalizing the degraded surrounding biota, being precursors to the list of more secondary documents that proved to be valuable sources of factual clarification. Results. The experience of didactic use related to Leme’s memory, rescued from the interviews and experiences of the interviewed people, allows a better evaluation of military attitudes of conservation and cataloging of effective military participation in environmental operations. The valorization of the fortress system, an important cultural heritage, corroborates actions aimed at tourism activities, preservation of memory, environmental education and environmentally conscious interventions.
Relaxation of the aorta during hypoxia is impaired in chronically hypertensive rats.

We investigated mechanisms by which hypoxia produces relaxation of the aorta and tested the hypothesis that these mechanisms are altered during chronic hypertension. Tension of thoracic aortae from normotensive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) was measured in an organ bath under control conditions and at two levels of hypoxia. In WKY rats, mild and severe hypoxia produced relaxation of the aortae (precontracted with phenylephrine) by 33 +/- 4% and 82 +/- 3%, respectively (mean +/- SEM). Removal of endothelium or administration of NG-nitro-L-arginine (10(-4) mol/L), an inhibitor of nitric oxide synthase, abolished relaxation of the aortae in response to mild hypoxia but did not affect relaxation during severe hypoxia. Glibenclamide (10(-6) mol/L), an inhibitor of potassium channels, attenuated relaxation of the aortae during mild and severe hypoxia by 49 +/- 16% and 74 +/- 4%, respectively. In SHRSP, mild hypoxia produced little relaxation of the aortae (3 +/- 4%, P < .05 compared with WKY). Indomethacin did not increase relaxation to mild hypoxia in SHRSP, which suggests that a cyclooxygenase-derived contracting factor does not contribute to impaired relaxation. Severe hypoxia relaxed the aortae by 86 +/- 4% in SHRSP, and glibenclamide inhibited this response by 60 +/- 9%. These findings suggest that relaxation of the aorta in response to mild hypoxia in WKY rats is mediated primarily by endothelium-derived relaxing factor, and the response to mild hypoxia is markedly impaired in SHRSP. (ABSTRACT TRUNCATED AT 250 WORDS)
Pushing the boundaries of school-university partnerships: Engaging the community

The editors of the journal conclude this issue with a call to action. We call on those who do the work of PDS to reflect on and examine how we can better engage all three groups of stakeholders – university, school, and community – to better serve students at all levels. Creation of third spaces focused on engaging the community and advocacy efforts that advance the profession are essential to strengthening Professional Development Schools and Systems. It is in these spaces and communities where we see partnerships continue to move towards mutually beneficial action.
Retrospective clinical evaluation of an internal tube-in-tube dental implant after 4 years, with special emphasis on peri-implant bone resorption.

PURPOSE A clinical evaluation of the long-term survival rate of three subtypes of a dental tube-in-tube implant with special emphasis on peri-implant bone resorption was conducted and is presented here. MATERIALS AND METHODS A retrospective follow-up examination of patients treated with tube-in-tube implants between August 2001 and August 2005 was conducted. For patients available for clinical recall, success criteria according to Albrektsson and Buser were evaluated. Differences in peri-implant bone resorption with regard to implant subtype and depth of implant placement (supracrestal or crestal) were calculated via the Student t test. RESULTS One hundred twenty-seven patients were provided with a total of 382 Camlog implants. Of the implants placed, 239 were root-line (RL), 129 were screw-line (SL), and 14 were cylindric. One hundred four patients with 318 implants could be contacted. In 59 cases, bony augmentation was performed. After an average time in situ of 32 months (range, 8 to 56 months), 307 of 318 surveyed implants (96.5%) remained in function. Six implants were lost as a result of absence of osseointegration, four following peri-implantitis, and one owing to hypesthesia. Two patients with eight implants have died since 2005, and 21 patients with 47 implants could not be contacted. In 75 patients with 240 implants, clinical success rates were 94% (Albrektsson) and 97% (Buser). A significant difference in bone resorption was found between RL and SL implants (P < .0001). Implants that had been placed supracrestally showed significantly less bone resorption than crestally inserted implants, both overall and in subgroup analyses (RL, P = .015; SL, P < .0001). CONCLUSION The internal tube-in-tube implant system showed promising long-term results. Significantly less bone resorption was seen for RL implants as well as for implants that were placed supracrestally.
C-reactive protein and sleep-disordered breathing.

STUDY OBJECTIVES Over a 2-month period, to evaluate serum levels of C-reactive protein (CRP) in new patients with obstructive sleep apnea syndrome (OSAS), upper airway resistance syndrome (UARS), and absence of important comorbidity, as well as in normal controls. DESIGN Cross-sectional analysis. SETTING Sleep disorders clinic. PATIENTS 239 successively monitored subjects: 156 subjects were diagnosed with OSAS, 39 with UARS, and 54 controls. INTERVENTIONS none. MEASUREMENTS AND RESULTS Clinical information (neurologic, general medical, and otolaryngology examination), body mass index, neck circumference, hip-waist ratio, Epworth Sleepiness Scale, 3 fatigue scales, Sleep Disorders Questionnaire, serum CRP, and polysomnography were collected. Analysis of variance indicated a significant difference between the groups for diastolic blood pressure, respiratory disturbance index, lowest SaO2, and body mass index. The mean serum CRP level was normal in all 3 groups. Only 15 (14 OSAS and 1 UARS) out of 239 subjects had high serum CRP values. CRP levels were significantly correlated with body mass index, esophageal pressures, hip-waist ratio, neck circumference, and blood pressure. Only body mass index was significantly associated with high CRP values; multiple regression showed: adjusted R2 = 0.115, beta = 0.345, P <. 001. When men and women were considered separately, body mass index was again significantly associated with high CRP levels. CONCLUSION Obesity is a risk factor for high serum CRP levels in patients with sleep-disordered breathing, as in the general population.
Observation Scales for Pain Assessment in Older Adults With Cognitive Impairments or Communication Difficulties

Background: Several pain observation scales have been developed to accurately assess and manage pain in older adults with severe cognitive impairments, communication difficulties, or both. Objective: To review relevant pain observation scales and the psychometric qualities of these scales. Methods: The literature was searched for articles reporting the use of a pain observation scale in an empirical study and describing psychometric properties in older adults with cognitive impairments, communication difficulties, or both. Results: Thirteen pain observation scales were included. Scales differed in numbers of items, types of categories, and psychometric properties. Facial expression, vocalization, motor behavior, and social behavior or mood are categories present in most of the scales. In terms of reliability and validity, however, most studies are too limited or incomplete to allow definite conclusions to be drawn about usefulness in daily practice. Discussion: As different methods of evaluating reliability and validity were used, and different aims (e.g., type of pain) were pursued, the available scales cannot be compared easily. Nevertheless, a few are promising, given preliminary results. These should be examined further on psychometric properties and usefulness in different populations because optimal pain assessment is necessary for efficient and effective pain treatment.
Life history adjustments to intestinal inflammation in a gut nematode

ABSTRACT Many parasitic nematodes establish chronic infections. This implies a finely tuned interaction with the host immune response in order to avoid infection clearance. Although a number of immune interference mechanisms have been described in nematodes, how parasites adapt to the immune environment provided by their hosts remains largely unexplored. Here, we used the gastrointestinal nematode Heligmosomoides polygyrus to investigate the plasticity of life history traits and immunomodulatory mechanisms in response to intestinal inflammation. We adopted an experimental model of induced colitis and exposed worms to intestinal inflammation at two different developmental stages (larvae and adults). We found that H. polygyrus responded to intestinal inflammation by up-regulating the expression of a candidate gene involved in the interference with the host immune response. Worms infecting mice with colitis also had better infectivity (earlier adult emergence in the intestinal lumen and higher survival) compared with worms infecting control hosts, suggesting that H. polygyrus adjusted its life history schedule in response to intestinal inflammation. Summary: Phenotypic plasticity of life history traits in a nematode can be an effective mechanism to adapt to intestinal inflammation.
Role of Nucleotides Immediately Flanking the Transcription-Regulating Sequence Core in Coronavirus Subgenomic mRNA Synthesis

ABSTRACT The generation of subgenomic mRNAs in coronavirus involves a discontinuous mechanism of transcription by which the common leader sequence, derived from the genome 5′ terminus, is fused to the 5′ end of the mRNA coding sequence (body). Transcription-regulating sequences (TRSs) precede each gene and include a conserved core sequence (CS) surrounded by relatively variable sequences (5′ TRS and 3′ TRS). Regulation of transcription in coronaviruses has been studied by reverse-genetics analysis of the sequences immediately flanking a unique CS in the Transmissible gastroenteritis virus genome (CS-S2), located inside the S gene, that does not lead to detectable amounts of the corresponding mRNA, in spite of its canonical sequence. The transcriptional inactivity of CS-S2 was genome position independent. The presence of a canonical CS was not sufficient to drive transcription, but subgenomic synthesis requires a minimum base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) provided by the CS and its adjacent nucleotides. A good correlation was observed between the free energy of TRS-L and cTRS-B duplex formation and the levels of subgenomic mRNA S2, demonstrating that base pairing between the leader and body beyond the CS is a determinant regulation factor in coronavirus transcription. In TRS mutants with increasing complementarity between TRS-L and cTRS-B, a tendency to reach a plateau in ΔG values was observed, suggesting that a more precise definition of the TRS limits might be proposed, specifically that it consists of the central CS and around 4 nucleotides flanking 5′ and 3′ the CS. Sequences downstream of the CS exert a stronger influence on the template-switching decision according to a model of polymerase strand transfer and template switching during minus-strand synthesis.