Miracle-dz/UniFAR-FTUs huggingface dataset:
Sub-lethal temperature thresholds indicate acclimation and physiological limits in brook trout Salvelinus fontinalis.

Upper thermal tolerance of brook trout Salvelinus fontinalis was estimated using critical thermal maxima (CTmax ) experiments on fish acclimated to temperatures that span the species' thermal range (5-25°C). The CTmax increased with acclimation temperature, but plateaued in fish acclimated to 20°C, 23°C and 25°C. Plasma lactate was highest and the hepatosomatic index (IH ) was lowest at 23°C and 25°C, which suggests additional metabolic costs at those acclimation temperatures. Our results suggest that there is a sub-lethal threshold between 20°C and 23°C, beyond which the fish experience reduced physiological performance. This article is protected by copyright. All rights reserved.
Human remains from Ein Gev I, Jordan Valley, Israel

Le squelette d'une femme, âgee de 30 a 40 ans, a ete mis au jour sur le site prehistorique d'Ein Guev I, dans un contexte kebarien date par le С14 d'environ 13.750 av. J.C. En depit du mauvais etat de conservation des os et de l'absence des maxillaires, la presque totalite du squelette a pu etre consolide et etudie. Tant les caracteres metriques que morphologiques permettent de placer cet individu dans une population proto-mediterraneenne, tres semblable a celle des natoufiens.
Dynamics of the fragile X mental retardation protein correlates with cellular and synaptic properties in primary auditory neurons following afferent deprivation

Afferent activity dynamically regulates neuronal properties and connectivity in the central nervous system. The Fragile X mental retardation protein (FMRP) is an RNA‐binding protein that regulates cellular and synaptic properties in an activity‐dependent manner. Whether and how FMRP level and localization are regulated by afferent input remains sparsely examined and how such regulation is associated with neuronal response to changes in sensory input is unknown. We characterized changes in FMRP level and localization in the chicken nucleus magnocellularis (NM), a primary cochlear nucleus, following afferent deprivation by unilateral cochlea removal. We observed rapid (within 2 hr) aggregation of FMRP immunoreactivity into large granular structures in a subset of deafferented NM neurons. Neurons that exhibited persistent FMRP aggregation at 12–24 hr eventually lost cytoplasmic Nissl substance, indicating cell death. A week later, FMRP expression in surviving neurons regained its homeostasis, with a slightly reduced immunostaining intensity and enhanced heterogeneity. Correlation analyses under the homeostatic status (7–14 days) revealed that neurons expressing relatively more FMRP had a higher capability of maintaining cell body size and ribosomal activity, as well as a better ability to detach inactive presynaptic terminals. Additionally, the intensity of an inhibitory postsynaptic protein, gephyrin, was reduced following deafferentation and was positively correlated with FMRP intensity, implicating an involvement of FMRP in synaptic dynamics in response to reduced afferent inputs. Collectively, this study demonstrates that afferent input regulates FMRP expression and localization in ways associated with multiple types of neuronal responses and synaptic rearrangements.
Epitypification of Broomella vitalbae and Introduction of a Novel Species of Hyalotiella

Abstract Broomella and Hyalotiella are poorly known genera in Amphisphaeriaceae . Both genera are known from morphological descriptions, but lack molecular data, thus their generic placement and relationships with other genera are unclear. Three collections of Amphisphaeriaceae were made from dead twigs of Clematis in Italy, and two from Spartium species and were identified as Broomella and Hyalotiella species. In order to obtain a phylogenetic understanding of Broomella and Hyalotiella within the family Amphisphaeriaceae , we carried out a phylogenetic analysis based on LSU gene data. Results show that these five isolates represent two distinct genera. Based on both morphological and phylogenetic data, the three isolates form Clematis are shown to be conspecific with Broomella vitalbae . In this paper we designated an epitype with a sexual and asexual morph for B. vitalbae to stabilize the understanding of the genus. The two strains from Spartium fit within the generic concepts of Hyalotiella , but sequence data for Hyalotiella species are presently lacking. Hyalotiella spartii sp. nov. is introduced based on its host association and morphological characters.
Inhibition of neurogenic and thromboxane A2‐induced human prostate smooth muscle contraction by the integrin α2β1 inhibitor BTT‐3033 and the integrin‐linked kinase inhibitor Cpd22

Prostate smooth muscle contraction is critical for etiology and treatment of lower urinary tract symptoms in benign prostatic hyperplasia (BPH). Integrins connect the cytoskeleton to membranes and cells to extracellular matrix, what is essential for force generation in smooth muscle contraction. Integrins are composed of different subunits and may cooperate with integrin‐linked kinase (ILK). Here, we examined effects of inhibitors for different integrin heterodimers and ILK on contraction of human prostate tissues.
Effect of sugar on the extrusion of maize grits and wheat flour

Summary The influence of added sucrose on the degree of expansion and extent of starch conversion on extrusion processing of wheat flour and maize grits has been reported. Very different behaviour was found for the two cereal systems. In agreement with previous work, replacement of maize by sucrose at constant water content reduced the specific mechanical energy and as a consequence, reduced the degree of starch conversion and sectional expansion. In contrast, replacing wheat flour by sucrose even at levels as high as 20% of the flour weight had little effect. Possible causes discussed were less efficient plasticization of wheat flour by sucrose compared with maize grits at low water contents, a specific role for gluten and the larger particle size of maize grits compared with wheat flour.
Plant responses to fertilization and exclusion of grazers on an arctic tundra heath

This study investigated the impacts of fertilization and grazing by Norwegian lemmings (Lemmus lemmus), grey-sided voles (Clethrionomys rufocanus), and reindeer (Rangifer tarandus) on a diverse tundra plant community dominated by deciduous shrubs. Four out of eight study areas, having a size of 2500 m 2 each, were fertilized with a N-P-K fertilizer and four areas served as unfertilized controls. Two types of exclosures were used within each study area, one to exclude solely reindeer, and one to exclude both rodents and reindeer. Open, grazed plots served as controls. During 5 years following the fertilization event the changes in vegetation inside and outside the exclosures were monitored using a point frequency method. The densities of rodents on the fertilized and unfertilized areas were investigated by live trapping and by counting nests of overwintering individuals. Reindeer do not graze on the study area during the growing season but migrate through this area in autumn and spring. Fertilization increased the abundance of vascular plants while grazing by reindeer and rodents decreased the abundance of vascular plants significantly on both fertilized and unfertilized areas. Rodents preferred clearly the fertilized areas during winter, decreasing the abundance of Vaccinium myrtillus and Vaccinium vitis-idaea, while very little grazing occurred during summer. Graminoids showed the strongest positive response to fertilization and dominated the plant community on ungrazed plots, while winter grazing by both reindeer and rodents significantly decreased the abundance of graminoids. Deciduous shrubs (Betula nana, Vaccinium myrtillus) increased slightly but significantly due to fertilization and evergreen dwarf shrubs showed no response to fertilization. However, the use of functional growth forms for predicting the responses of nutrient enrichment and grazing must be questioned, as responses to fertilization as well as preferences by herbivores were shown to be species-specific rather than uniform within functional groups based on plant growth forms.
Risk of QTc prolongation among cancer patients treated with tyrosine kinase inhibitors

QTc interval prolongation can lead to life‐threatening complications such as Torsade de Pointes (TdP), ventricular tachycardia (VT) and sudden cardiac death (SCD). It can occur with tyrosine kinase inhibitors (TKIs) but comparative real‐world analyses on the incidence and complication rates are scarce. We retrospectively reviewed all cancer patients treated with TKI therapy at Mayo Clinic between January 2005 and December 2018 and had at least two ECGs (before and after TKI). For each TKI type, we determined the administration rate and incidence of QTc prolongation. QTc prolongation was defined as a corrected QT interval (by Fridericia formula) ≥450 ms in men and ≥470 ms in women. A total of 618 cancer patients were included with 902 TKI administrations, of which 654 (72.5%) were accounted for by pazopanib, sunitinib, imatinib, nilotinib and dasatinib. QTc prolongation (any grade) was reported in 28.8%, most commonly with nilotinib (38.7%) and dasatinib (41.7%). A QTc interval ≥500 ms and a QTc increase ≥60 ms was documented in 46 and 63 administrations, respectively. Life‐threatening toxicity was seen in 14 cases (5.4% of QTc prolongation cases) including VT in 9, SCD in 3 and TdP in two administrations. The response to QTc prolongation was: discontinuation in 68%, dose reduction in 13.5%, temporary hold in 8.1% and no action in 10.4%. In conclusion, QTc prolongation with TKI therapy is very common (∼1/3 of cases) and in 5% (1.7% overall) associated with life‐threatening complications. These data support recommendations for careful ECG monitoring in cancer patients undergoing TKI therapy.
Mechanisms of mutagenesis induced by DNA lesions: multiple factors affect mutations in translesion DNA synthesis

Abstract Environmental mutagens lead to mutagenesis. However, the mechanisms are very complicated and not fully understood. Environmental mutagens produce various DNA lesions, including base-damaged or sugar-modified DNA lesions, as well as epigenetically modified DNA. DNA polymerases produce mutation spectra in translesion DNA synthesis (TLS) through misincorporation of incorrect nucleotides, frameshift deletions, blockage of DNA replication, imbalance of leading- and lagging-strand DNA synthesis, and genome instability. Motif or subunit in DNA polymerases further affects the mutations in TLS. Moreover, protein interactions and accessory proteins in DNA replisome also alter mutations in TLS, demonstrated by several representative DNA replisomes. Finally, in cells, multiple DNA polymerases or cellular proteins collaborate in TLS and reduce in vivo mutagenesis. Summaries and perspectives were listed. This review shows mechanisms of mutagenesis induced by DNA lesions and the effects of multiple factors on mutations in TLS in vitro and in vivo.
Challenges and opportunities in insomnia disorder

Abstract Background Insomnia disorder is a prevalent, often unrecognized condition that affects millions. This clinical disorder is characterized by difficulty initiating or maintaining sleep over a sustained period. In fact, insomnia disorder affects much more than sleep; it increases the risk of developing serious medical and psychiatric comorbidities and can exacerbate existing conditions. The association between insomnia disorder and serious medical and psychiatric comorbidities are complex and directionality is not yet fully understood. There remain gaps in the treatment landscape for insomnia disorder. Methods We performed a narrative review of the published literature to identify challenges, unmet needs, and burden associated with insomnia disorder. Results In this article, we describe the substantial burden that insomnia disorder poses on patients, the healthcare system, and society in the US. This article explores the factors attributable to this burden including limited provider knowledge, inadequate treatment options, and unknown long-term impacts of off-label treatments. Conclusions Several recommendations are proposed to address these challenges and improve patient outcomes through efforts to: (1) establish the societal value of treatment; (2) improve the clinical understanding of insomnia disorder; and (3) prioritize development of and access to effective treatments that do not pose addiction potential or tolerability issues.
Examining Belief in a Just World, Religious Worldviews, and Self-Esteem Within the Framework of Terror Management Theory: Mortality Salient and Nonmortality Salient Organizations

To sustain their lives has always been the main motivation of all the creatures, especially human beings. Just as there is always beginning of life, there is also an end of it for all living species. Human being is the only species that is aware of their mortality. According to terror management theory (TMT), this awareness causes some sort of anxiety. Human being, by their nature, do not want to be worried and want to cope with the anxiety in different ways. This study aims to test belief in a just world, religious worldviews, and self-esteem within the framework of TMT hypotheses in both mortality salient (n = 104) and nonmortality salient (n = 102) organizations. In each organization, half of the participants were reminded about death (experimental condition) and the other half about toothache (control condition). The required data for this study were collected by utilizing Life Satisfaction Scale, The Multidimensional Mortality Awareness Measure, Positive and Negative Affect Schedule, Belief in a Just World Scale, Self-Esteem Scale, Religious Worldviews Scale, and personal information form. Results indicated that there are no significant differences for self-esteem and religious worldviews between mortality salient and nonmortality salient samples, whereas there are significant mean differences for personal/general belief in a just world. The findings of this study are discussed within the framework of TMT literature.
Thermal activity thresholds of the parasitic wasp Lysiphlebus testaceipes and its aphid prey: implications for the efficacy of biological control

Adult parasitoids Lysiphlebus testaceipes Cresson (Hymenoptera: Aphidiidae) lose locomotory function and enter chill coma at significantly lower temperatures (−0.1 and −8.0 °C, respectively) than their second‐instar hosts, the black bean aphid Aphis fabae Scop. (Hemiptera: Aphididae) (5.6 and 2.3 °C, respectively). Parasitoids are also more heat tolerant, stop walking at 41.4 °C, with heat coma at 44.1 °C, than the aphid (39.1 and 43.0 °C, respectively). Furthermore, across a range of temperatures (0–20 °C), L. testaceipes has considerably faster walking speeds than A. fabae. These data are discussed in relation to the climatic conditions under which L. testaceipes would be an effective control agent, and the likelihood of establishment and spread in northern European climates.
Expression of SOAT1 in adrenocortical carcinoma and response to mitotane monotherapy: an ENSAT multicenter study.

CONTEXT Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20% and adverse drug effects are frequent. To date there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1) which leads to endoplasmic reticulum stress and cell death in ACC cells. OBJECTIVE To investigate SOAT1 protein expression as a marker of treatment response to mitotane. PATIENTS 231 ACC patients treated with single agent mitotane as adjuvant (n=158) or advanced disease therapy (n=73) from twelve ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded (FFPE) specimens. SETTING Retrospective study at 12 ACC referral centers. MAIN OUTCOME MEASURE recurrence-free survival (RFS), progression-free survival (PFS), disease-specific survival (DSS). RESULTS 61/135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumour stage and Ki67 index, RFS (HR=1.07, 95% CI 0.61-1.85, p=0.82) and DSS (HR=1.30, 95% CI 0.58-2.93, p=0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR=1.34, 95% CI 0.63-2.84, p=0.45) and DSS (HR=0.72, 95% CI 0.31-1.70, p=0.45) were comparable and response rates not significantly different. CONCLUSIONS SOAT1 expression was not correlated with clinical endpoints RFS, PFS and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival.
Glycine receptors and GABAA receptor α1 and γ2 subunits during the development of mouse hypoglossal nucleus

In the hypoglossal nucleus, GABA and glycine mediate inhibition at separate or mixed synapses containing glycine receptors (GlyRs) and/or GABAA receptors (GABAARs). The functional development of mixed inhibitory synapses depends on the brain area studied, but their relative proportion to total synapses generally decreases with time. We have determined the sequential process of inhibitory synapse maturation in the hypoglossal nucleus in vivo. Immunocytochemistry and confocal microscopy were used for codetection of VIAAT, the common presynaptic vesicular transporter of glycine and GABA, GlyRs, GABAAR α1 and γ2 subunits, and gephyrin, the scaffold protein implicated in the synaptic localization of inhibitory receptors. In E17 embryos, GlyRs were already clustered while GABAAR α1 and γ2 subunit immunoreactivity (IR) displayed both diffuse and clustered patterns. Quantitative analysis at this stage revealed that the majority of GlyR clusters were apposed to VIAAT‐IR accumulation and that 30% of them colocalized with γ2GABAAR clusters. This proportion increased with age to 50% at P30. GlyR clusters that did not colocalize with γ2GABAAR clusters were associated with GABAAR γ2 diffuse IR. Interestingly, the percentage of GlyR clusters surrounded by GABAAR γ2 diffuse IR decreased with age, while GlyR clusters colocalized with γ2GABAAR clusters increased. The developmental coclustered pattern of gephyrin and GABAAR α1 and γ2 subunits paralleled the coclustered pattern of GlyRs and GABAAR α1 and γ2 subunits. Our results indicate that the proportion of GlyR‐GABAAR coclusters increases until adulthood. A developmental sequence of the postsynaptic events is proposed in which diffuse extrasynaptic GABAARs accumulate at inhibitory synapses to form postsynaptic clusters, most of them being colocalized with GlyR clusters in the adult.
Internalization of nanoparticles into spiral ganglion cells

The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatments for conditions such as Meniere’s disease, tinnitus, schwannomas of the ear, and for improving hearing. The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new approaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific delivery can be achieved by functionally “addressed” nanostructures loaded with a therapeutic molecule. In the present study, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles (NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwann dissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse video microscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistry for the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studied in more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently (Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied using fluorescence microscopy. The study demonstrates that DiI-loaded NPs can be internalized into guinea pig SG neurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reduced viability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into the cytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen in axons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in small vesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could lead to the development of more specialized NPs, targeting only SG neurons or Schwann cells.
Effects of ripening conditions on the texture of Gouda cheese

Summary The effects of ripening temperature, type of packaging film and storage period before packaging were related to the degree of proteolysis and the texture of Gouda cheese, so as to determine the optimum ripening conditions. Gouda cheeses from a local plant were subjected to different ripening conditions. A factorial design of 23× 5 was used, where the three factors selected in two levels were: (1) time of storage before packaging, 4 and 10 days, (2) ripening temperature, 10 and 20 °C and (3) plastic film, BK1 and BK5 (Grace, Quilmes, Argentina). Ripening time was a fourth factor analyzed; sampling times were 15, 25, 35, 49 and 70 days after production. Cheeses traditionally ripened (without packaging) were also analyzed. Water content and pH were determined. Nonprotein nitrogen (soluble in 12% trichloracetic acid (TCA)) was quantified by the Kjeldhal method. Cheese texture was analyzed by compression and relaxation tests which were done by using an Instron Universal Testing Machine (Instron Corp., Canton, MA, USA). The pH and water content of cheeses which ripened at 20 °C were lower than the corresponding ones ripened at 10 °C. Only ripening time and temperature had a significant effect on water content, nonprotein nitrogen concentration and rheological parameters. Results show that texture properties of Gouda cheese ripened in plastic films with low gaseous permeability are similar to those of traditionally ripened Gouda. Texture development was accelerated by increasing the storage temperature.
Mate Preference and Mating Behavior of Male Helicoverpa zea (Lepidoptera: Noctuidae) Infected with the Sexually Transmitted Insect Virus Hz-2V

Abstract The affect of Hz-2V (a.k.a. gonad-specific virus) virus infection on the reproductive physiology and behavior of infected adult Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) males was examined. Virus-infected males responded and flew to calling healthy and infected females at about the same rate. Although infected males were slower in approaching healthy females and attempting to mate compared with healthy males, infected males did make sexual contacts with females that could serve to transmit virus. Unlike matings with healthy males, which result in the cessation of calling, females that had made sexual contact with infected males continued to exhibit calling behavior and were receptive to mates. Although calling behavior of both healthy and infected females was inhibited by injecting extracts of reproductive tissues from healthy males, extracts of reproductive tissues from infected males inhibited female calling to a lesser degree and for an additional night compared with extracts from healthy males. The results presented here further demonstrate the ability of Hz-2V to alter the physiology and behavior of infected insects in ways that could serve to facilitate virus transmission.