Miracle-dz/UniFAR-FTUs huggingface dataset:
Key role of 5‐HT1A receptors in the modulation of the neuronal network underlying the respiratory rhythm generation in lampreys

In mammals, 5‐HTexcitatory respiratory effects imply 5‐HT1A receptor‐mediated disinhibition of pre‐Bötzinger complex neurons. In the lamprey, 5‐HT1A receptors are involved in the neural control of locomotion, but their role in the respiratory regulation, particularly at the level of the putative respiratory rhythm generator, the paratrigeminal respiratory group (pTRG), is not known. We here investigate the respiratory function of inhibitory 5‐HT1A receptors within the pTRG of the isolated brainstem of the adult lamprey. The 5‐HT1A receptor agonists either bath applied or microinjected into the pTRG did not cause significant effects. However, the selective 5‐HT1A receptor antagonist (S)‐WAY 100135 bath applied or microinjected into the pTRG induced depressing respiratory effects or even apnoea, thus revealing that 5‐HT exerts a 5‐HT1A receptor‐mediated potent tonic influence on respiration and contributes to maintain baseline levels of respiratory activity. Microinjections of strychnine or bicuculline, either alone or in combination, into the pTRG prevented (S)‐WAY 100135‐induced apnoea. In addition, immunohistochemical studies corroborate the present findings suggesting that 5‐HT1A receptors are widely expressed in close apposition to the soma of glycine‐immunoreactive cells located within the pTRG region. The results show that in the lamprey respiratory network, 5‐HT exerts a tonic influence on respiration by a potent inhibitory control on both GABAergic and glycinergic mechanisms. The observed disinhibitory effects resemble the excitatory respiratory modulation exerted by 5‐HT1A receptor‐mediated inhibition of glycinergic and/or GABAergic neurons present in mammals, supporting the notion that some features of the neuronal network subserving respiratory rhythm generation are highly conserved throughout phylogeny.
Dielectric properties of developing rabbit brain at 37°C

The dielectric properties of developing rabbit brain were measured at 37 degrees C between 10 MHz and 18 GHz using time domain and frequency domain systems. The results show a variation with age of the dielectric properties of brain. An analysis of the data suggests that the water dispersion in the brain of newly born animals can be represented by a Debye equation. This dispersion increases in complexity with age, and there is evidence of a smaller additional relaxation process centered around 1 GHz. It is concluded that the principal contribution to this subsidiary dispersion region arises from water of hydration.
Versatile Movements of Liquid Metal Droplet under Electrostatic Actuation in Alkaline Solutions

The gallium-based eutectic liquid metal alloys exhibit unique properties of deformability, excellent electrical conductivity and low vapour pressure. The liquid metal-based circuits’ element or actuator have drawn considerable attention in stretchable electronics and microelectromechanical (MEMS) actuators. Yet, the motion of the liquid metal within the electrolyte needs to be precisely regulated to satisfy application requirements. Herein, we investigated the locomotion of liquid metal within the alkaline aqueous solution under electrostatic actuation. The relationship between the travelling speed of the liquid metal slug and the relative influential parameters, such as the voltage amplitude and frequencies of the applied electric field, electrolyte concentration, electrodes distance and the liquid metal volume, were experimentally characterized. A travelling speed up to 20.33 mm/s was obtained at the applied voltage of 4 Vpp at 150 Hz at 6 V DC offset. Finally, the frequency-dependent liquid metal marble movements were demonstrated, namely oscillation and forward locomotion while oscillating. The oscillation frequency was determined by the frequency of the applied alternate current (AC) signal. The remarkable transportation and oscillating characteristic of the liquid metal marble under the electrostatic actuation may present potentials towards the development of flexible electronics and reconfigurable structures.
Reducing facial dynamics’ speed during speech enhances attention to mouth in children with autism spectrum disorder: An eye-tracking study

Abstract Facial movements of others during verbal and social interaction are often too rapid to be faced and/or processed in time by numerous children and adults with autism spectrum disorder (ASD), which could contribute to their face-to-face interaction peculiarities. We wish here to measure the effect of reducing the speed of one's facial dynamics on the visual exploration of the face by children with ASD. Twenty-three children with ASD and 29 typically-developing control children matched for chronological age passively viewed a video of a speaker telling a story at various velocities, i.e., a real-time speed and two slowed-down speeds. The visual scene was divided into four areas of interest (AOI): face, mouth, eyes, and outside the face. With an eye-tracking system, we measured the percentage of total fixation duration per AOI and the number and mean duration of the visual fixations made on each AOI. In children with ASD, the mean duration of visual fixations on the mouth region, which correlated with their verbal level, increased at slowed-down velocity compared with the real-time one, a finding which parallels a result also found in the control children. These findings strengthen the therapeutic potential of slowness for enhancing verbal and language abilities in children with ASD.
Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein

The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called COVID-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be ‘preactivated’ and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.
Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review

Background Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB). Objective To determine the IP associated with LTBI, compared to active TB and individuals not infected by M. tuberculosis published in literature. Methods We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, Mycobacterium tuberculosis, cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without M. tuberculosis infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants' information, diagnostic criteria, IP, detection methods, and biases were collected. Results We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF-α, CSF3, CSF2, CCL1 [I-309], IL-7, TGF-β1, CCL3 [MIP-1α], sIL-2R, TNF-β, CCL7 [MCP-3], IFN-α, fractalkine, I-TAG, CCL8 [MCP-2], CCL21 [6Ckine], PDGF, IL-22, VEGF-A, LXA4, PGE2, PGF2α, sCD163, sCD14, and 15-Epi-LXA4), five were elevated in LTBI (IL-5, IL-17F, IL-1, CCL20 [MIP-3α], and ICAM-1), and two substances were increased among uninfected individuals (IL-23 and basic FGF). We found high heterogeneity between studies including failure to account for the time/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity. Conclusions It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO CRD42017073289.
Centrosome Abnormalities and Polyploidy in Murine Mammary Carcinomas with Different Degrees of Hormone Responsiveness

Abstract Centrosome amplification leads to aberrant mitosis, giving rise to aneuploidy and it has been associated with poor prognosis in human cancers. This study aimed to evaluate the relationship between polyploidy, centrosome abnormalities, and response to endocrine treatment in progestin-induced mouse mammary carcinomas. We found cells with three or more centrosomes in the polyploid tumors. The endocrine unresponsive tumors showed a higher average number of centrosomes per cell than the responsive tumors. The results suggest an association between polyploidy and centrosome amplification with the resistance to endocrine therapy in this luminal breast cancer model.
RESPIRATORY DEFICIENT MUTANTS OF BOTTOM BREWER'S YEAST II. TECHNOLOGICAL PROPERTIES OF SOME RD MUTANTS

Five spontaneous respiratory deficient mutants of one strain of bottom brewer's yeast were studied, being chosen for differences in their cytochrome system, and in rates of growth and fermentation. Pilot plant experiments showed that these 5 mutants differed from the original type also in the utilization of nitrogen compounds, in the sequence of utilization of sugars, and in the pattern of sedimentation. The beers prepared using these mutants were more aromatic, had higher contents of nitrogen compounds and of anthocyanogens, lower contents of most free amino acids and substantially lower contents of higher aliphatic alcohols. Their pH values were higher as well as their buffering capacities. One of the 5 mutants studied produced beer of better flavour than the original type.
THE EFFECT OF A MICROSPORIDIAN PARASITE ON THE DEVELOPMENT, REPRODUCTION, AND MORTALITY OF THE SPRUCE BUDWORM, CHORISTONEURA FUMIFERANA (CLEM.)

Infection of the spruce budworm, Choristoneura fumiferana (Clem.), by the microsporidian parasite Perezia fumiferanae Thorn, retards both larval and pupal development and reduces pupal weight, fecundity, and adult longevity. These effects are more pronounced among the female insects. There is no evidence that the parasite affects male fertility, mate choice, or the fertility of eggs produced. The parasite causes some mortality, most of which occurs before the fifth instar. Among larvae infected orally, mortality seems to be related to the size of the initial dose. Mortality occurs equally in both sexes. The development and survival of the first instar and overwintering second instar are not affected by the parasite. It is suggested that the parasite causes most of the observed results by reducing the insect's ability to assimilate its food. Mortality, however, is believed to be due to the destruction of the mid-gut or Malpighian tubules.
Recurrent Selection for Adaptation of Erysiphe graminis f. sp. hordei to Partial Resistance and the Effect of Environment on Expression of Partial Resistance of Barley

Five isolates of powdery mildew were subjected to recurrent selection on partially resistant barley cultivars and tested at intervals for adaptation to overcome partial resistance. A trend towards adaptation to the recurrent host was observed in infection frequency data, but biomass per colony, measured using sterol cell-wall determinations and enzyme linked immunosorbent assay, was not greatly affected. The expression of partial resistance was examined after seedling growth under two different environmental regimes. Significant interactions with both overall resistance expression and latent period were detected using infection frequency data, and the effects were both cultivar and isolate dependent. Variability between single colony derivatives of an isolate, which had previously shown adaptation to a partially resistant cultivar, was detected in infection frequency data indicating instability and a non-nuclear component to adaptation.
Anti-HIV drugs promote β-amyloid deposition and impair learning and memory in BALB/c mice

Abstract Objectives: Growing evidence suggested that antiretroviral (ARV) drugs may promote amyloid beta (Aβ) accumulation in HIV-1-infected brain and the persistence of HIV-associated neurocognitive disorders (HANDs). It has also been shown that lipid peroxidation upregulates β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) expression and subsequently promotes Aβ peptide production. In the present study, we examined whether chronic exposure to the anti-HIV drugs tenofovir disoproxil fumarate (TDF) and nevirapine induces lipid peroxidation thereby promoting BACE1 and Aβ generation and consequently impair cognitive function in mice. Methods: TDF or nevirapine was orally administered to female BALB/c mice once a day for 8 weeks. On the 7th week of treatment, spatial learning and memory were assessed using the Morris water maze test. The levels of lipid peroxidation, BACE1, amyloid β 1-42 (Aβ1-42) and Aβ deposits were measured in the hippocampal tissue upon completion of treatment. Results: Chronic administration of nevirapine induced spatial learning and memory impairment in the Morris water maze test, whereas TDF did not have an effect. TDF and nevirapine administration increased hippocampal lipid peroxidation and Aβ1-42 concentration. Nevirapine further upregulated BACE1 expression and Aβ deposits. Conclusion: Our results suggest that chronic exposure to TDF and nevirapine contributes to hippocampal lipid peroxidation and Aβ accumulation, respectively, as well as spatial learning and memory deficits in mice even in the absence of HIV infection. These findings further support a possible link between ARV drug toxicity, Aβ accumulation and the persistence of HANDs.
Red deer (Cervus elaphus) spatial use in the Italian Alps: home range patterns, seasonal migrations, and effects of snow and winter feeding

The spatial behaviour of 20 red deer was analyzed for the first time in the Italian Alps using radio-telemetry, from 1995 to 1997 in the Tarvisio forest, and from 1995 to 1999 in the Susa valley. Two distinct strategies of spatial behaviour were displayed in both study areas, i.e., migratory and stationary. Migratory red deer showed significantly larger annual home ranges, as each year they reached distant summer areas located at higher altitudes. Stationary red deer, instead, remained in the same areas throughout the year, with the exception of summer movement to neighbouring areas at higher altitude. As a consequence of these movements towards and from summer areas, spring and autumn migratory home ranges were significantly larger, while stationary home ranges recorded during spring, summer, and autumn were comparable in size. In winter home range sizes were limited in all monitored deer whenever snow cover reduced their mobility. Migratory red deer movements proved to be markedly affected by snowfall, with their monthly altitudes inversely correlated with snow presence on the ground. Stationary deer vertical movements proved less affected by presence of snow, as they reached lower altitude during summer. During winter, migratory red deer showed a greater use of the Tarvisio supplementary feeding stations, the only study site where this practice was in use. Migratory individuals probably adopted an opportunistic strategy, using the Alpine meadows at higher altitudes during the summer and the feeding stations during the winter, even if the use of feeding stations may be the end result of a poorer knowledge of trophic availability inside the winter areas. During the winter all the monitored deer used the same areas; food supply should be avoided in order not to promote high deer concentration and to reduce the risk of heavy forest browsing.
Effects of Deltamethrin on the Ultrastructures of the Root Meristem Cells of Allium cepa

Abstract The EC 50 value of commercially formulated deltamethrin (Decis 2.8% EC) was determined to be 0.87 ppm against Allium root growth. Root meristem cells were exposed to deltamethrin (0.5–2 ppm) for 6 to 24 h and examined by transmission electron microscopy. Deltamethrin induced various morphological abnormalities in the cell wall, plasma membrane, and Golgi apparatus dictyosomes. The microfibrillar arrangement of cell wall appeared to be amorphous in treated cells. The plasma membrane showed extensive dehiscence from the cell wall. The stacked cisternal membrane of dictyosomes were seem to be degenerated and the vesicles emanating from the dictyosomes were found to be accumulated around the degenerated dictyosome remnants. Sporadic dilation of dictyosome cisternae was also observed in the treated cells. Most nuclei in treated cells were observed to contain condensed chromatin material. The number of microtubles in the preprophase band was significantly reduced in 24 h treatment. Deltamethrin frequently disturbed the parallel array of spindle microtubules in metaphase cells. Telophase cells exposed to deltamethrin revealed incomplete, if not irregular, cell wall formation. Present findings suggest that the action of deltamethrin on microtubules is to an extent similar to that of microtubule depolymerizing drugs, which is the primary cause of toxicity leading to the induction of various mitotic aberrations. However, induction of structural and functional aberrations in the Golgi apparatus dictyosomes indicates the effect of deltamethrin on intercisternal elements and microfilaments, which possibly keeps the cisternal stack intact and directs the intracellular transport of vesicles.
Near-infrared nerve-binding fluorophores for buried nerve tissue imaging

Small-molecule near-infrared nerve contrast agents were developed to enable nerve visualization at depth, improving nerve-sparing during surgery. Avoiding hitting a nerve Fluorescence-guided surgery uses contrast agents to identify nerves intraoperatively; however, existing agents have poor tissue specificity and high background or permit only surface-level imaging. Wang et al. developed near-infrared nerve-binding fluorophores that could be administered locally or systemically for deep nerve visualization. Testing the oxazine-based contrast agents in murine and porcine models identified buried nerves during laparoscopic surgery. These contrast agents could help avoid injuring nerves during surgery. Nerve-binding fluorophores with near-infrared (NIR; 650 to 900 nm) emission could reduce iatrogenic nerve injury rates by providing surgeons precise, real-time visualization of the peripheral nervous system. Unfortunately, current systemically administered nerve contrast agents predominantly emit at visible wavelengths and show nonspecific uptake in surrounding tissues such as adipose, muscle, and facia, thus limiting detection to surgically exposed surface-level nerves. Here, a focused NIR fluorophore library was synthesized and screened through multi-tiered optical and pharmacological assays to identify nerve-binding fluorophore candidates for clinical translation. NIR nerve probes enabled micrometer-scale nerve visualization at the greatest reported tissue depths (~2 to 3 mm), a feat unachievable with previous visibly emissive contrast agents. Laparoscopic fluorescent surgical navigation delineated deep lumbar and iliac nerves in swine, most of which were invisible in conventional white-light endoscopy. Critically, NIR oxazines generated contrast against all key surgical tissue classes (muscle, adipose, vasculature, and fascia) with nerve signal-to-background ratios ranging from ~2 (2- to 3-mm depth) to 25 (exposed nerve). Clinical translation of NIR nerve-specific agents will substantially reduce comorbidities associated with surgical nerve damage.
Hepatic Transferrin Plays a Role in Systemic Iron Homeostasis and Liver Ferroptosis.

Although the serum-abundant metal-binding protein transferrin (encoded by the Trf gene) is synthesized primarily in the liver, its function in the liver is largely unknown. Here, we generated hepatocyte-specific Trf knockout mice (Trf-LKO), which are viable and fertile but have impaired erythropoiesis and altered iron metabolism. Moreover, feeding Trf-LKO mice a high-iron diet increased their susceptibility to develop ferroptosis-induced liver fibrosis. Importantly, we found that treating Trf-LKO mice with the ferroptosis inhibitor ferrostatin-1 potently rescued liver fibrosis induced by either high dietary iron or carbon tetrachloride (CCl4) injections. In addition, deleting hepatic Slc39a14 expression in Trf-LKO mice significantly reduced hepatic iron accumulation, thereby reducing ferroptosis-mediated liver fibrosis induced by either high dietary iron diet or CCl4 injections. Finally, we found that patients with liver cirrhosis have significantly lower levels of serum transferrin and hepatic transferrin, as well as higher levels of hepatic iron and lipid peroxidation compared to healthy controls. Taken together, these data indicate that hepatic transferrin plays a protective role in maintaining liver function, providing a possible therapeutic target for preventing ferroptosis-induced liver fibrosis.
Seizure detection using heart rate variability: A prospective validation study

Although several validated seizure detection algorithms are available for convulsive seizures, detection of nonconvulsive seizures remains challenging. In this phase 2 study, we have validated a predefined seizure detection algorithm based on heart rate variability (HRV) using patient‐specific cutoff values. The validation data set was independent from the previously published data set. Electrocardiography (ECG) was recorded using a wearable device (ePatch) in prospectively recruited patients. The diagnostic gold standard was inferred from video–EEG monitoring. Because HRV‐based seizure detection is suitable only for patients with marked ictal autonomic changes, we defined responders as the patients who had a>50 beats/min ictal change in heart rate. Eleven of the 19 included patients with seizures (57.9%) fulfilled this criterion. In this group, the algorithm detected 20 of the 23 seizures (sensitivity: 87.0%). The algorithm detected all but one of the 10 recorded convulsive seizures and all of the 8 focal impaired awareness seizures, and it missed 2 of the 4 focal aware seizures. The median sensitivity per patient was 100% (in nine patients all seizures were detected). The false alarm rate was 0.9/24 h (0.22/night). Our results suggest that HRV‐based seizure detection has high performance in patients with marked autonomic changes.