Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Genomics of Marine Fishes: Next-Generation Prospects and Challenges

Over the past few years, technological advances have facilitated giant leaps forward in our ability to generate genome-wide molecular data, offering exciting opportunities for gaining new insights into the ecology and evolution of species where genomic information is still limited. Marine fishes are valuable organisms for advancing our understanding of evolution on historical and contemporary time scales, and here we highlight areas in which research on these species is likely to be particularly important in the near future. These include possibilities for gaining insights into processes on ecological time scales, identifying genomic signatures associated with population divergence under gene flow, and determining the genetic basis of phenotypic traits. We also consider future challenges pertaining to the implementation of genome-wide coverage through next-generation sequencing and genotyping methods in marine fishes. Complications associated with fast decay of linkage disequilibrium, as expected for species with large effective population sizes, and the possibility that adaptation is associated with both soft selective sweeps and polygenic selection, leaving complex genomic signatures in natural populations, are likely to challenge future studies. However, the combination of high genome coverage and new statistical developments offers promising solutions. Thus, the next generation of studies is likely to truly facilitate the transition from population genetics to population genomics in marine fishes. This transition will advance our understanding of basic evolutionary processes and will offer new possibilities for conservation and management of valuable marine resources.
Lack of consistency between five definitions of nonprogression in cohorts of HIV-infected seroconverters

Objective:To identify appropriate criteria for characterizing HIV-infected nonprogressors. Design:Five definitions were compared as follows: (1) last CD4 count > 500×106/l; (2) two most recent CD4 counts > 500×106/l; (3) calculated CD4 count based on linear regression > 500×106/l; (4) CD4 slope ≥ 0 with no antiretroviral use; (5) all CD4 counts > 500×106/l, decline in CD4 slope < 5 cells per year, no antiretroviral use. Participants:Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion. Main outcome measures:Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded. Results:Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1–3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1–3. None of the definitions classified the same subjects as nonprogressors at any timepoint. Conclusions:Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.
Development of Bronchial Hyperresponsiveness During Childhood

Bronchial hyperresponsiveness (BHR) produces the characteristic pathological abnormalities seen in asthma and clearly plays a central role in the pathophysiology of asthma. The presence of BHR has been demonstrated in infants with asthma, as has the possibility of BHR persisting through the childhood period. The level of BHR may not only reflect the state of the airways, as a marker of airway dysfunction, but may also predict the persistent prognosis of the disease. Thus, measurement of BHR may provide important information about the symptoms and lung function in children with asthma. In view of multiple pathophysiological mechanisms, BHR does not seem to have a single cause. Many potential confounding variables, such as age, gender, and genetic status, and some environmental factors, such as allergens, infections, and pollutants, could be responsible for the establishment of childhood BHR. There may be differences between the mechanisms that induce transient BHR and the mechanisms that induce persistent BHR. Also, there may be differences between the causes that induce BHR in the infantile period and the causes that maintain persistent BHR during childhood asthma. There is also disagreement as to the most suitable method to measure BHR in children, especially in infants. The assessment of BHR in young children has not been uniformly successful, and measurements of BHR changes over the childhood period are associated with a number of problems. To resolve these problems, there may be two ways to study childhood BHR. One is to use age-matched specific techniques to clarify the precise BHR in each age group; the other is to use simple techniques that can be performed over the childhood period on a large number of subjects. In studies of infantile respiratory dysfunction the ultimate goal is to establish a simple, noninvasive method by which measurements of respiratory function may be obtained in infants. Further investigations and acceptable methods will be needed to clarify the mechanisms involved in the establishment of asthma throughout the childhood period.
Global Expression Profile of Biofilm Resistance to Antimicrobial Compounds in the Plant-Pathogenic Bacterium Xylella fastidiosa Reveals Evidence of Persister Cells

ABSTRACT Investigations of biofilm resistance response rarely focus on plant-pathogenic bacteria. Since Xylella fastidiosa is a multihost plant-pathogenic bacterium that forms biofilm in the xylem, the behavior of its biofilm in response to antimicrobial compounds needs to be better investigated. We analyzed here the transcriptional profile of X. fastidiosa subsp. pauca in response to inhibitory and subinhibitory concentrations of copper and tetracycline. Copper-based products are routinely used to control citrus diseases in the field, while antibiotics are more widely used for bacterial control in mammals. The use of antimicrobial compounds triggers specific responses to each compound, such as biofilm formation and phage activity for copper. Common changes in expression responses comprise the repression of genes associated with metabolic functions and movement and the induction of toxin-antitoxin systems, which have been associated with the formation of persister cells. Our results also show that these cells were found in the population at a ca. 0.05% density under inhibitory conditions for both antimicrobial compounds and that pretreatment with subinhibitory concentration of copper increases this number. No previous report has detected the presence of these cells in X. fastidiosa population, suggesting that this could lead to a multidrug tolerance response in the biofilm under a stressed environment. This is a mechanism that has recently become the focus of studies on resistance of human-pathogenic bacteria to antibiotics and, based on our data, it seems to be more broadly applicable.
E-Cadherin Promoter Hypermethylation in Preneoplastic and Neoplastic Skin Lesions

E-cadherin is a calcium-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and plays an important role in maintaining epithelial stability. E-cadherin is widely regarded as a prognostic marker in many types of human cancers. The inactivation of the E-cadherin gene is linked to increased potential for tumor invasiveness and distant metastasis. We previously demonstrated reduced expression of E-cadherin protein immunohistochemically in invasive squamous cell carcinomas of the skin as compared with adjacent normal skin. An epigenetic alteration in association with promoter hypermethylation is one important mechanism of gene silencing. In the present study, we analyze the E-cadherin gene promoter hypermethylation in preneoplastic and neoplastic skin lesions to determine whether epigenetic alteration of the E-cadherin gene also plays an important role in cutaneous squamous carcinogenesis. A total of 33 cases was examined for evidence of E-cadherin promoter hypermethylation, and these consist of nine cases of spongiotic dermatitis as nonneoplastic skin control, nine cases of actinic keratosis, eight cases of squamous cell carcinoma in situ, and seven cases of invasive squamous cell carcinoma. Promoter hypermethylation of the E-cadherin gene was detected in 6 of 7 cases (85%) of invasive squamous cell carcinoma, 4 of 8 cases (50%) of squamous cell carcinoma in situ, 4 of 9 cases (44%) of actinic keratosis, and 2 of 9 cases (22%) of nonneoplastic skin. We conclude that E-cadherin promoter hypermethylation occurs frequently and may represent an important mechanism of E-cadherin inactivation in cutaneous preneoplastic and neoplastic lesions. The frequencies of E-cadherin promoter hypermethylation appear to be correlated with more advanced stage of squamous carcinogenesis in skin.
How the Bible Became a Book: The Textualization of Ancient Israel

1. How the Bible became a book 2. The numinous power of writing 3. Writing and the state 4. Writing in the early Israelite State 5. Hezekiah and the spread of writing 6. Josiah and the text revolution 7. How the Torah became a text 8. Writing in exile 9. Scripture in the shadow of the temple 10. Epilogue 11. Further reading.
Effect of Different Parthenogenetic Activation Methods on the Developmental Competence of in vitro Matured Porcine Oocytes

The aim of this study was to investigate the effect of electrical pulse, ethanol, and ionomycin combined with cycloheximide (CHX), cytochalasin B (CB), and 6-dimethylaminopurine (6-DMAP) on parthenogenetic developmental competence of in vitro matured porcine oocytes. In experiment 1, oocytes were treated with direct current electrical pulse (DC pulse) and then incubated in the NCSU-23 medium supplemented with CHX, 6-DMAP, CB + CHX, and CB + 6-DMAP for 6 h, respectively. The rate of blastocyst development in DC pulse + CB + 6-DMAP group was significantly higher than those in other groups (42.4% vs 23.9% ∼ 35.8%; P < 0.05); however, there were no differences in both of the cleavage rate and the cell number of blastocysts among four groups. In experiment 2, oocytes were treated with NCSU-23 medium containing 20 μM ionomycin for 40 min and then incubated in the NCSU-23 medium supplemented with CHX, 6-DMAP, CB + CHX and CB + 6-DMAP for 6 h, respectively. The rates of cleavage and blastocyst development in ionomycin + 6-DMAP group were higher than those obtained in other groups (66.2% vs 46.3% ∼ 57.3%; 22.3% vs 7.4% ∼ 16.1%; P < 0.05). In experiment 3, the activation effects of ethanol combined with 6-DMAP, CHX, CB + 6-DMAP and CB + CHX were investigated. The rates of cleavage and blastocyst development in ethanol + CB + 6-DMAP group were significantly higher than those in other groups (55.5% vs 42% ∼ 46.2%; 18.0% vs 7.1% ∼ 11.9%; P < 0.05). In experiment 4, the optimal activation protocols in each group plus DC pulse + ionomycin + 6-DMAP were compared. The results showed the rates of cleavage in DC pulse + CB + 6-DMAP group and ionomycin + 6-DMAP were higher than those in ethanol + CB + 6-DMAP and DC pulse + ionomycin + 6-DMAP (73.8–74.4% vs 56.5–57.5%; P < 0.05), but the blastocyst development only in DC pulse + CB + 6-DMAP group was significantly higher than that in other groups (34.1% vs 13.4% ∼ 22.3%; P < 0.05). Total cell number of blastocysts in the group of DC pulse + ionomycin + 6-DMAP was higher than that in other groups (34.1 vs 25.3–27.2; P < 0.05). In conclusion, DC pulse, ethanol, CB, and 6-DMAP all affected the parthenogenesis of porcine oocytes matured in vitro, but their combination of DC pulse + CB + 6-DMAP showed the best result in both of cleavage and blastocyst development.
Conventional Versus Accelerated Collagen Cross-Linking for Keratoconus

Abstract: Collagen cross-linking (CXL) is a procedure that primarily aims to increase corneal stiffness. Although used for a variety of conditions, it is most commonly applied to the treatment of keratoconus. Collagen cross-linking involves irradiation of the cornea with ultraviolet A (UVA) irradiation after it has been soaked with riboflavin (vitamin B), a photosensitizer. In conventional treatment, based on the Dresden protocol, a minimum corneal thickness threshold of 400 &mgr;m is recommended and UVA (370 nm) irradiation of 3 mW/cm2 irradiance is applied for 30 min, resulting in a cumulative dose of 5.4 J/cm2. Evidence presented in this review shows that conventional CXL stabilizes the vision and corneal topographic parameters in the majority of treated patients, with only a small failure rate. It has a good safety profile with no endothelial cell loss and a small risk of corneal infiltration and infection. To reduce the treatment duration, accelerated protocols of similar efficacy have been sought. In accelerated protocols, UVA irradiation of higher irradiance, typically 9 mW/cm2, is applied for a shorter time, typically 10 min. The evidence, limited to small studies with short follow-up, shows that they may also stabilize the vision and the ectasia, with no additional safety concerns highlighted. Randomized controlled studies are, however, required to confirm the encouraging results and noninferiority to conventional treatment.
Evaluation and Management of Increased Intracranial Pressure

Purpose of Review: Persistent elevation of intracranial pressure (ICP) can lead to cerebral ischemia, brain herniation, and possibly death. Understanding the fundamental mechanism that contributes to the rise in ICP and recognizing the specific intracranial compartment involved (brain, CSF, or blood) can lead to early diagnosis and effective treatment. This article reviews the conceptual approach to a patient with elevated ICP. Recent Findings: The overall goal for patients with intracranial hypertension is to lower ICP below 20 mm Hg and to maintain cerebral perfusion pressure (CPP) between 60 mm Hg and 90 mm Hg to provide sufficient cerebral perfusion. Commonly used therapeutic interventions to lower ICP include decompressive surgery, osmotherapy, hyperventilation, barbiturate-induced metabolic suppression, and hypothermia; however, the selection of these interventions must be tailored to each patient by considering the particular diagnosis and intracranial pathophysiology. Emerging evidence suggests that cerebral autoregulation may fail at excessively high CPP (CPP greater than 100 mm Hg) as well as at low CPP (CPP less than 60 mm Hg) and that maximal cerebral autoregulation capacity may be achieved at an optimal CPP of 70 mm Hg to 90 mm Hg. Summary: Increased ICP is a neurologic emergency that requires immediate intervention. However, the treatment itself is not without risk; thus, the risks and benefits of medical and surgical intervention must be carefully evaluated and individualized for each patient.
Expression of the (recombinant) endogenous immunoglobulin heavy-chain locus requires the intronic matrix attachment regions

The elements which regulate gene expression have traditionally been identified by their effects on reporter genes which have been transfected into cell lines or animals. It is generally assumed that these elements have a comparable role in expression of the corresponding endogenous locus. Nevertheless, several studies of immunoglobulin heavy-chain (IgH) gene expression have reported that the requirements for expressing IgH-derived transgenes differ from the requirements for expression of the endogenous IgH locus. Thus, although expression of transgenes requires multiple elements from the J(H)-C mu intron--the E mu core enhancer, the matrix attachment regions (MARs) which flank E mu, and several switch-associated elements--B-cell lines in which expression of the endogenous heavy-chain gene is maintained at the normal level in the absence of these intronic elements have occasionally been reported. Gene targeting offers an alternative method for assessing regulatory elements, one in which the role of defined segments of endogenous genes can be evaluated in situ. We have applied this approach to the IgH locus of a hybridoma cell line, generating recombinants which bear predetermined modifications in the functional, endogenous mu heavy-chain gene. Our analysis indicates the following. (i) Ninety-eight percent of the expression of the recombinant endogenous mu gene depends on elements in the MAR-E mu-MAR segment. (ii) Expression of the recombinant mu gene depends strongly on the MARs of the J(H)-C mu intron but not on the adjoining E mu core enhancer and switch regions; because our recombinant cell lines bear only a single copy of the mu gene, our results indicate that mu expression is activated by MAR elements lying within that same mu transcription unit. (iii) The MAR segment includes at least one activating element in addition to those defined previously by the binding of presumptive activating proteins in the nuclear matrix. (iv) Close association of the MARs with the E mu enhancer is not required for MAR-stimulated expression. (v) The other MARs in the IgH locus do not in their normal context provide the requisite MAR function.
Processing Slow and Fast Motion in Children With Autism Spectrum Conditions

Consistent with the dorsal stream hypothesis, difficulties processing dynamic information have previously been reported in individuals with autism spectrum conditions (ASC). However, no research has systematically compared motion processing abilities for slow and fast speeds. Here, we measured speed discrimination thresholds and motion coherence thresholds in slow (1.5 deg/sec) and fast (6 deg/sec) speed conditions in children with an ASC aged 7 to 14 years, and age‐ and ability‐matched typically developing children. Unexpectedly, children with ASC were as sensitive as typically developing children to differences in speed at both slow and fast reference speeds. Yet, elevated motion coherence thresholds were found in children with ASC, but in the slow stimulus speed condition only. Rather than having pervasive difficulties in motion processing, as predicted by the dorsal stream hypothesis, these results suggest that children with ASC have a selective difficulty in extracting coherent motion information specifically at slow speeds. Understanding the effects of stimulus parameters such as stimulus speed will be important for resolving discrepancies between previous studies examining motion coherence thresholds in ASC and also for refining theoretical models of altered autistic perception. Autism Res 2013, 6: 531–541. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Enhancement of Electricity Generation and Sulfide Removal in Microbial Fuel Cells with Lead Dioxide Catalyzed Cathode

Lead dioxide catalyzed cathode (PbO2) which has high overpotential and electrode potential with low cost was tested in microbial fuel cells (MFCs) for sulfide removal in this study, compared with traditional platinum based carbon cathode (Pt/C). The maximum power density of 997.26±±20.20 mW/m2 was realized, with sulfide removal efficiency as high as 88.73±±4.37%, both showing advantage to Pt/C cathode. The products of sulfide oxidation were examined and elemental sulfur was found to be generated during energy recovery. The MFC with PbO2 cathode got higher elemental sulfur generation than that with Pt/C cathode. Pb(II) was not detected in cathodic electrolyte during operation, indicating that PbO2 was an effective and environmental-friendly cathodic catalyst to Pt in MFCs for electricity generation and sulfide removal.
Diabetes mellitus and increased risk of cholangiocarcinoma: a meta-analysis

Diabetes mellitus (DM) has been reported to be associated with an increased risk of several types of cancers. However, its relationship with cholangiocarcinoma (CC), which includes intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), remains unclear. We conducted a meta-analysis to assess the association between diabetes and the risk of CC (including ICC and ECC). We identified studies by a literature search of Medline (from 1 January 1966) and Embase (from 1 January 1974), through 30 November 2010, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model. A total of 15 articles (10 case–control and five cohort studies) were included in this study. The number of reports on DM and risk of specific cancer were as follows: CC (n=5), ECC (n=9), and ICC (n=9). Compared with those without diabetes, individuals with diabetes had an increased risk of CC (summary RRs, 1.60; 95% CI, 1.38–1.87; P=0.992 for heterogeneity), ECC (summary RRs, 1.63; 95% CIs, 1.29–2.05; P=0.005 for heterogeneity), and ICC (summary RRs, 1.97; 95% CIs, 1.57–2.46; P=0.025 for heterogeneity). The funnel plot revealed no evidence for publication bias concerning diabetes and the risk of CC (including ICC and ECC). These findings strongly support the positive link between DM and the increased risk of CC (including ICC and ECC).
Aggregation of a slow-folding mutant of a beta-clam protein proceeds through a monomeric nucleus.

Mechanistic understanding of protein aggregation, leading either to structured amyloid fibrils or to amorphous inclusion body-like deposits, should facilitate the identification of potential therapeutic intervention strategies for the devastating amyloid-based diseases. Here we focus on the in vitro aggregation of a slow-folding mutant of the beta-clam protein, cellular retinoic acid-binding protein I (P39A CRABP I), which forms inclusion bodies when expressed in Escherichia coli. Aggregation was monitored by observing the fluorescence of a fluorescein-based biarsenical dye (FlAsH) that ligates to a tetra-Cys motif, here incorporated into a flexible Omega-loop. The fluorescence signal of FlAsH on the tetra-Cys-containing P39A CRABP I is sensitive to whether this protein is native or unfolded, and was used in combination with other techniques to follow aggregate formation. The aggregation time course is compatible with a nucleation-dependent polymerization model, and detailed kinetic analysis showed that the energetically unfavorable nucleus is monomeric. A similar conclusion was reached previously for poly(Gln) species [Chen, S. , Ferrone, F. A. , and Wetzel, R. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 11884-11889] and points to an unfavorable equilibrium between the misfolded intermediate and the bulk pool of monomers as causative in aggregation. The P39A mutation, which removes a helix-stop signal, may slow closure of the beta-barrel in P39A CRABP I relative to the wild type, leaving it vulnerable to aggregation. Wide-angle X-ray scattering showed that the amorphous aggregates formed by the aggregation-prone intermediates of P39A CRABP I contain predominantly beta-strands structured in a lamellar fashion with 10.03 A spacing between adjacent beta-sheets.
Low molecular weight heparin decreases the permeability of glomerular endothelial cells when exposed to pre‐eclampsia serum in vitro

Low molecular weight heparin (LMWH) has been used to treat certain kidney diseases such as pre‐eclampsia, in which extensive levels of proteinuria are associated with dysfunction of glomerular endothelium. In our study, we investigated whether LMWH could affect the permeability of and ET‐1 expression in human glomerular endothelial cells (GEnC) incubated with pre‐eclampsia serum.