Miracle-dz/UniFAR-FTUs huggingface dataset:
Absence of A3Z3-Related Hypermutations in the env and vif Proviral Genes in FIV Naturally Infected Cats

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) proteins comprise an important family of restriction factors that produce hypermutations on proviral DNA and are able to limit virus replication. Vif, an accessory protein present in almost all lentiviruses, counteracts the antiviral A3 activity. Seven haplotypes of APOBEC3Z3 (A3Z3) were described in domestic cats (hap I–VII), and in-vitro studies have demonstrated that these proteins reduce infectivity of vif-defective feline immunodeficiency virus (FIV). Moreover, hap V is resistant to vif-mediated degradation. However, studies on the effect of A3Z3 in FIV-infected cats have not been developed. Here, the correlation between APOBEC A3Z3 haplotypes in domestic cats and the frequency of hypermutations in the FIV vif and env genes were assessed in a retrospective cohort study with 30 blood samples collected between 2012 and 2016 from naturally FIV-infected cats in Brazil. The vif and env sequences were analyzed and displayed low or undetectable levels of hypermutations, and could not be associated with any specific A3Z3 haplotype.
The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation

The time-dependent rate I(t) of origin firing per length of unreplicated DNA presents a universal bell shape in eukaryotes that has been interpreted as the result of a complex time-evolving interaction between origins and limiting firing factors. Here, we show that a normal diffusion of replication fork components towards localized potential replication origins (p-oris) can more simply account for the I(t) universal bell shape, as a consequence of a competition between the origin firing time and the time needed to replicate DNA separating two neighboring p-oris. We predict the I(t) maximal value to be the product of the replication fork speed with the squared p-ori density. We show that this relation is robustly observed in simulations and in experimental data for several eukaryotes. Our work underlines that fork-component recycling and potential origins localization are sufficient spatial ingredients to explain the universality of DNA replication kinetics.
Ontogeny of the osteocranium in the African catfish, Clarias gariepinus Burchell (1822) (Siluriformes: Clariidae): Ossification sequence as a response to functional demands

The ontogeny of the bony skull of the African catfish, Clarias gariepinus, is studied from initial ossification until a complete skull is formed. The ossification sequence in C. gariepinus seems to be related to the functional demands that arise in a developing larva. Early ossification of the opercular bone coincides with the initiation of opercular skin movements. Early ossifications involve several dentulous bones, formed shortly before the transition phase from endogenous to exogenous feeding. The enlarging branchiostegal membrane becomes supported by the gradual adding of branchiostegal rays. Parasphenoid ossification may be related to protection of the brain during prey transport, whereas the several hyoid bones, including the parurohyal, are formed in relation to the increasing loads exerted onto the tendons of the sternohyoideus and consequently onto the hyoid bar. Overall skull reinforcement occurs almost simultaneously, with a whole set of perichondral bones arising especially at places of high mechanical load. The suspensorium becomes protected against dislocation in an anteroposterior direction through a ligamentous connection, which even becomes partially ossified, forming the sesamoid entopterygoid. Later, the cranial lateral‐line system becomes enclosed by a set of gutters, which close, frequently becoming plate‐like later in ontogeny. The brain also becomes covered dorsally. Additional dentition (prevomeral tooth plates) formation seems to coincide with formation of the opercular four‐bar system, as well as with the time the digestive system becomes completely functional. Eventually, unossified regions between the bones become closed off, fortifying and completely covering the skull. J. Morphol. 235:183–237, 1998. © 1998 Wiley‐Liss, Inc.
Metaphase kinetochore movements are regulated by kinesin-8 motors and microtubule dynamic instability

During metaphase, sister chromatids are connected to microtubules extending from the opposite spindle poles via kinetochores to protein complexes on the chromosome. Kinetochores congress to the equatorial plane of the spindle and oscillate around it, with kinesin-8 motors restricting these movements. Yet, the physical mechanism underlying kinetochore movements is unclear. We show that kinetochore movements in the fission yeast Schizosaccharomyces pombe are regulated by kinesin-8-promoted microtubule catastrophe, force-induced rescue, and microtubule dynamic instability. A candidate screen showed that among the selected motors only kinesin-8 motors Klp5/Klp6 are required for kinetochore centering. Kinesin-8 accumulates at the end of microtubules, where it promotes catastrophe. Laser ablation of the spindle resulted in kinetochore movement toward the intact spindle pole in wild-type and klp5Δ cells, suggesting that kinetochore movement is driven by pulling forces. Our theoretical model with Langevin description of microtubule dynamic instability shows that kinesin-8 motors are required for kinetochore centering, whereas sensitivity of rescue to force is necessary for the generation of oscillations. We found that irregular kinetochore movements occur for a broader range of parameters than regular oscillations. Thus, our work provides an explanation for how regulation of microtubule dynamic instability contributes to kinetochore congression and the accompanying movements around the spindle center.
A Novel Deltaflexivirus that Infects the Plant Fungal Pathogen, Sclerotinia sclerotiorum, Can Be Transmitted Among Host Vegetative Incompatible Strains

Various mycoviruses have been isolated from Sclerotinia sclerotiorum. Here, we identified a viral RNA sequence contig, representing a novel virus, Sclerotinia sclerotiorum deltaflexivirus 2 (SsDFV2), from an RNA_Seq database. We found that SsDFV2 was harbored in the hypovirulent strain, 228, which grew slowly on potato dextrose agar, produced a few sclerotia, and could not induce typical lesions on detached rapeseed (Brassica napus) leaves. Strain 228 was also infected by Botrytis porri RNA Virus 1 (BpRV1), a virus originally isolated from Botrytis porri. The genome of SsDFV2 comprised 6711 nucleotides, excluding the poly (A) tail, and contained a single large predicted open reading frame encoding a putative viral RNA replicase. Phylogenetic analysis demonstrated that SsDFV2 is closely related to viruses in the family Deltaflexiviridae; however, it also differs significantly from members of this family, suggesting that it may represent a new species. Further we determined that SsDFV2 could be efficiently transmitted to host vegetative incompatible individuals by dual culture. To our best knowledge, this is the first report that a (+) ssRNA mycovirus can overcome the transmission limitations of the vegetative incompatibility system, a phenomenon that may facilitate the potential use of mycoviruses for the control of crop fungal diseases.
HYPNOTIZABILITY AND PAIN MODULATION: A Body–Mind Perspective

Abstract The study investigated whether the cardiac activity and cognitive–emotional traits sustained by the behavioral inhibition/activation system (BIS/BAS) may contribute to hypnotizability-related pain modulation. Nociceptive stimulation (cold-pressor test) was administered to healthy participants with high (highs) and low (lows) hypnotizability in the presence and absence of suggestions for analgesia. Results showed that heart rate increased abruptly at the beginning of nociceptive stimulation in all participants. Then, only in highs heart rate decreased for the entire duration of hand immersion. During stimulation with suggestions of analgesia, pain threshold negatively correlated with heart rate. BIS/BAS activity partially accounted for the observed hypnotizability-related differences in the relation between cardiac interoception and pain experience.
Use of a Binocular Optical Coherence Tomography System to Evaluate Strabismus in Primary Position

Importance Current clinical methods for assessing strabismus can be prone to error. Binocular optical coherence tomography (OCT) has the potential to assess and quantify strabismus objectively and in an automated manner. Objective To evaluate the use of a binocular OCT prototype to assess the presence and size of strabismus. Design, Setting, and Participants Fifteen participants with strabismus were recruited in 2016 as part of the EASE study from Moorfields Eye Hospital National Health Service Foundation Trust, London, England, and 15 healthy volunteers underwent automated anterior segment imaging using the binocular OCT prototype. All participants had an orthoptic assessment, including alternating prism cover test (APCT), before undergoing imaging. Simultaneously acquired pairs of OCT images, captured with 1 eye fixating, were analyzed using ImageJ (National Institutes of Health) to assess the presence and angle of strabismus. Main Outcomes and Measures The direction and size of strabismus measured using binocular OCT was compared with that found using APCT. Results The median age for participants with strabismus was 55 years (interquartile range [IQR], 33-66.5 years) and for the healthy group, 50 years (IQR, 41-59 years); 15 participants (50%) were women, and 25 participants (83.3%) were white. The median magnitude of horizontal deviation was 20[INCREMENT] (IQR, 13-35[INCREMENT]) and for vertical deviation, 3[INCREMENT] (IQR, 0-5[INCREMENT]). Binocular OCT imaging correctly revealed the type and direction of the deviation in all 15 participants with strabismus, including horizontal and vertical deviations. The APCT and OCT measurements were strongly correlated for the horizontal (Pearson r = 0.85; 95% CI, 0.60-0.95; P < .001) and vertical (r = 0.89; 95% CI, 0.69-0.96; P < .001) deviations. In the healthy cohort, 9 of 15 participants (60%) had a latent horizontal deviation on APCT results (median magnitude 2[INCREMENT], range 2-4[INCREMENT]). Six (40%) had orthophoria. Horizontal deviations were observed on OCT imaging results in 12 of the 15 participants (80%), and a vertical deviation was visible in 1 participant (6.7%). Conclusions and Relevance These findings suggest that binocular anterior segment OCT imaging can provide clinicians with a precise measurement of strabismus. The prototype can potentially incorporate several binocular vision tests that will provide quantitative data for the assessment, diagnosis, and monitoring of ocular misalignments.
Proximity and Matthew Effect in co-authorship pattern of Iranian top universities

Co-authorship is used to measure scholarly collaborations of countries, institutions, and individuals. It refers to the process in which two or more authors or researchers collaborate with each other to create a joint-work through collaboration methods and channels. Although many studies have been conducted to analyze the individual or field co-authorships in Iran, a little have concerned the organisational co-authorships in this country. This study aims to analyze organisational coauthorships among Iranian top universities based on proximity rule and Matthew effect. Data were limited to published articles affiliated to top universities in Iran and extracted from the Web of Science (WoS) database. The co-authorship matrix of these universities was shaped and their relationships were mapped. The “National Co-Authorship Index”, which is the rate of scholarly coauthorships among universities of a country, was calculated. Results show that geographic proximity has important and strong role in co-authorships of Iranian top universities. Top universities tend to collaborate with universities of similar ranking and probably this result confirms the Matthew effect in the collaborations of Iranian top universities. Also, the role of collocation or proximity has been drawn on Iran map. Finally, some suggestions were made to improve the co-authorship system of Iranian universities.
Habitual exercise training in older adults offsets the age-related prolongation in leg vasodilator kinetics during single-limb lower body exercise.

We tested the hypothesis that aging is associated with prolonged leg vasodilator kinetics and habitual exercise training in older adults improves these responses relative to untrained older adults. Additionally, we examined the relationship between contraction-induced rapid onset vasodilation (ROV) and vasodilator kinetics. Young ( n = 10), older untrained ( n = 13), and older trained ( n = 14) adults performed single and rhythmic knee-extension contractions at 20% and 40% work-rate maximum (WRmax). Femoral artery diameter and mean blood velocity were measured by Doppler ultrasound. Vascular conductance (VC; ml·min-1·mmHg-1) was calculated using blood flow (ml/min) and mean arterial pressure (mmHg). The primary outcome was the kinetic response (mean response time; MRT), modeled using an exponential model, expressed as the number of duty cycles to change 63% of the steady-state amplitude. There were no age- or training-related differences in VC MRT between the groups at 20% WRmax. Older untrained adults exhibited prolonged VC MRT at 40% WRmax relative to young (37 ± 16 vs. 24 ± 10 duty-cycles; P < 0.05) and older trained adults (37 ± 16 vs. 23 ± 14 duty-cycles; P < 0.05). There were no differences in VC MRT between young and older trained adults at 40% WRmax ( P = 0.96). There were no associations between peak ROV and VC MRT at 20% or 40% WRmax ( r = -0.08 and 0.22; P = 0.67 and 0.20, respectively) in the group as a whole. Our data suggest 1) advancing age prolongs leg vasodilator kinetics; 2) habitual exercise training in older adults offsets this age-related prolongation; and 3) contraction-induced ROV is not related to vasodilator kinetics within a group of young and older adults. NEW & NOTEWORTHY Aging is associated with reductions in exercise hyperemia and vasodilation at the onset of exercise, as well as during steady-state exercise. Habitual endurance exercise training offsets these age-related reductions. We found that aging prolongs vasodilator kinetics in the leg of older untrained but not older trained adults. Finally, our results demonstrate that contraction-induced rapid vasodilation is not associated with vasodilator kinetics within the leg of young and older adults.
Comparison of teeth and dermal denticles (odontodes) in the teleost Denticeps clupeoides (Clupeomorpha)

The present work is a contribution to an extensive comparative structural and developmental study we have undertaken to understand the evolution of the dermal skeleton in osteichthyans. We have investigated the structure of developing and functional tooth‐like dermal denticles located on the head of Denticeps clupeoides, a clupeomorph, and compared their features to those of oral teeth. Morphological (scanning electron microscopy) and structural (light microscopy and transmission electron microscopy) observations clearly demonstrate that these small, sharp, conical and slightly backward‐oriented denticles are true odontodes, i.e., homologous to oral teeth. They are composed of a dentine cone surrounding a pulp cavity, the top being covered by a hypermineralized cap. These odontodes are attached to a circular pedicel of attachment bone by a ligament that mineralizes, and the attachment bone matrix merges with that of the bony support. The pedicel of attachment bone surrounds a vascular cavity that is connected to the pulp cavity which is devoid of blood vessels and of nerve endings. Once the odontode is functional, the deposition of collagen matrix (called circumpulpar dentine) continues against the dentine, ligament, and attachment bone surfaces, thereby provoking a narrowing of the pulp cavity. Odontodes are shed by resorption occurring at the base, but their pedicels of attachment bone persist at the bone surface and become embedded in the bone matrix, within which they are clearly visible. The oral teeth are similar in shape, size, and structure to the odontodes, and they show only small differences probably related to the different function of these elements: They are more firmly anchored to the attachment bone, and the amount of dentine is relatively smaller than in odontodes. Despite their different functions, this close structural agreement between teeth and odontodes in Denticeps suggests that 1) competent cells from the same (ecto)mesenchymal population might be involved and 2) the genetic control of the developmental processes could be identical. It is suggested that the odontode expression in extra‐oral positions is a relatively late novelty in this lineage. J. Morphol. 237:237–255, 1998. © 1998 Wiley‐Liss, Inc.
Sex Differences at the Time of Myectomy in Hypertrophic Cardiomyopathy

Background: One of the first clinically detectable alterations in heart function in hypertrophic cardiomyopathy (HCM) is a decline in diastolic function. Diastolic dysfunction is caused by changes in intrinsic properties of cardiomyocytes or an increase in fibrosis. We investigated whether clinical and cellular parameters of diastolic function are different between male and female patients with HCM at the time of myectomy. Methods and Results: Cardiac tissue from the interventricular septum of patients with HCM (27 women and 44 men) was obtained during myectomy preceded by echocardiography. At myectomy, female patients were 7 years older than male patients and showed more advanced diastolic dysfunction than men evident from significantly higher values for E/e′ ratio, left ventricular filling pattern, tricuspid regurgitation velocity, and left atrial diameter indexed for body surface. Whereas most male patients (56%) showed mild (grade I) diastolic dysfunction, 50% of female patients showed grade III diastolic dysfunction. Passive tension in HCM cardiomyocytes was comparable with controls, and myofilament calcium sensitivity was higher in HCM compared with controls, but no sex differences were observed in myofilament function. In female patients with HCM, titin was more compliant, and more fibrosis was present compared with men. Differences between female and male patients with HCM remained significant after correction for age. Conclusions: Female patients with HCM are older at the time of myectomy and show greater impairment of diastolic function. Furthermore, left ventricular and left atrial remodeling is increased in women when corrected for body surface area. At a cellular level, HCM women showed increased compliant titin and a larger degree of interstitial fibrosis.
Mir-34a-5p Mediates Cross-Talk between M2 Muscarinic Receptors and Notch-1/EGFR Pathways in U87MG Glioblastoma Cells: Implication in Cell Proliferation

Glioblastoma (GBM) is the most aggressive human brain tumor. The high growth potential and decreased susceptibility to apoptosis of the glioma cells is mainly dependent on genetic amplifications or mutations of oncogenic or pro-apoptotic genes, respectively. We have previously shown that the activation of the M2 acetylcholine muscarinic receptors inhibited cell proliferation and induced apoptosis in two GBM cell lines and cancer stem cells. The aim of this study was to delve into the molecular mechanisms underlying the M2-mediated cell proliferation arrest. Exploiting U87MG and U251MG cell lines as model systems, we evaluated the ability of M2 receptors to interfere with Notch-1 and EGFR pathways, whose activation promotes GBM proliferation. We demonstrated that the activation of M2 receptors, by agonist treatment, counteracted Notch and EGFR signaling, through different regulatory cascades depending, at least in part, on p53 status. Only in U87MG cells, which mimic p53-wild type GBMs, did M2 activation trigger a molecular circuitry involving p53, Notch-1, and the tumor suppressor mir-34a-5p. This regulatory module negatively controls Notch-1, which affects cell proliferation mainly through the Notch-1/EGFR axis. Our data highlighted, for the first time, a molecular circuitry that is deregulated in the p53 wild type GBM, based on the cross-talk between M2 receptor and the Notch-1/EGFR pathways, mediated by mir-34a-5p.
Effect of adding nalbuphine to intrathecal bupivacaine with morphine on postoperative nausea and vomiting and pruritus after elective cesarean delivery: a randomized double blinded study.

BACKGROUND The use of intrathecal morphine may result in serious side effects in parturients undergoing cesarean delivery. Nalbuphine, is a mu receptor antagonist and a ĸappa receptor agonist. Combinations of opioid agonist and agonist antagonist can decrease the incidence of opioid related side effects. We aimed to investigate the effect of adding nalbuphine, to intrathecal morphine on postoperative nausea and vomiting and pruritus after a cesarean delivery. METHODS Eighty parturient undergoing elective cesarean delivery under spinal anesthesia were randomized into two similar groups. Group 1: received 10 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine. Group 2: received as a group 1 plus 0.5 mg nalbuphine, with total volume 2.5 mL in both groups. Measurements: Data on the severity of nausea and vomiting were collected using a numerical rating scale and visual analogue scale was used to quantify pruritus. Onset and duration of sensory blockade, Visual Analog Scale for pain, the first time to ask for rescue analgesia and total rescue analgesic consumption were recorded. RESULTS Nausea and vomiting and pruritus severity scores and number of patients developed nausea and vomiting and pruritus were significantly lower (P<0.001) in group 2. Onset and duration of sensory block, time to first request for rescue analgesia, Visual Analog Scale for pain and paracetamol consumption showed no statistically differences between both groups (P>0.05). CONCLUSIONS We concluded that the addition of nalbuphine to intrathecal bupivacaine plus morphine significantly reduced the incidence and severity of postoperative nausea and vomiting and pruritus without affecting analgesic potency.
Microtubules and Microtubule-Associated Proteins.

Microtubules act as "railways" for motor-driven intracellular transport, interact with accessory proteins to assemble into larger structures such as the mitotic spindle, and provide an organizational framework to the rest of the cell. Key to these functions is the fact that microtubules are "dynamic. " As with actin, the polymer dynamics are driven by nucleotide hydrolysis and influenced by a host of specialized regulatory proteins, including microtubule-associated proteins. However, microtubule turnover involves a surprising behavior-termed dynamic instability-in which individual polymers switch stochastically between growth and depolymerization. Dynamic instability allows microtubules to explore intracellular space and remodel in response to intracellular and extracellular cues. Here, we review how such instability is central to the assembly of many microtubule-based structures and to the robust functioning of the microtubule cytoskeleton.