Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

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Zearalenone induces chromosome aberrations in mouse bone marrow: preventive effect of 17β-estradiol, progesterone and Vitamin E

The cytogenetic effect of zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, was evaluated in vivo, in mouse bone marrow cells, by assessing the percentage of cells bearing different chromosome aberrations. The studies included different conditions for animal treatment, as follows: (1) single intraperitoneal (ip) injection, (2) repeated ip injections, (3) pre-treatment for 24 h with Vitamin E (Vit E), and (4) pre-treatment for 4 h with 17β-estradiol (17β-Est) or progesterone (Prog). ZEN induced different types of chromosome aberrations, which was concentration-dependent (2–20 mg/kg bw). These doses corresponded to 0.4–4% of the LD₅₀ in the mouse. Interestingly, when the dose of ZEN (40 mg/kg) was fractionated into four equivalent doses (4 × 10 mg/kg bw), into three doses (15 + 10 + 15 mg/kg bw), or into two equivalent doses (2 × 20 mg/kg bw), given every 24 h, the percentage of chromosome aberrations increased significantly. This finding suggests that ZEN proceeds by reversible binding on receptors that could become saturated, and that it damages the chromosomes in a ‘hit and go’ manner. Furthermore, pre-treatment of animals with 17β-estradiol or progesterone significantly decreased the percentage of chromosome aberrations, suggesting that (i) these hormones bind to the same cytoplasmic receptors transported into the nucleus to elicit DNA damage, (ii) they may play a role in preventing chromosome aberrations induced by ZEN. Similarly, Vit E prevented these chromosome aberrations indicating that Vit E, previously reported to prevent most of the toxic effects induced by ZEN, may also bind to the same receptors.     

Thrombopoietic activity induced by blood withdrawal and administration of antithrombocyte serum in nephrectomized rats. Role of kidneys in the production of thrombopoietin

The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms.     

<Emphasis Type="Italic">In vitro</Emphasis> Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a constant driving force with maximum thermodynamic activity. The permeability coefficient (K _p), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K _p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10–12 are more effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity, which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%. In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety of penetration enhancers is a prime consideration.     

Psychiatric Molecular Genetics and the Ethics of Social Promises

A recent literature review of commentaries and ‘state of the art’ articles from researchers in psychiatric genetics (PMG) offers a consensus about progress in the science of genetics, disappointments in the discovery of new and effective treatments, and a general optimism about the future of the field. I argue that optimism for the field of psychiatric molecular genetics (PMG) is overwrought, and consider progress in the field in reference to a sample estimate of US National Institute of Mental Health funding for this paradigm for the years 2008 and 2009. I conclude that the amounts of financial investment in PMG is questionable from an ethical perspective, given other research and clinical needs in the USA.     

Effects of limited feeding of aflatoxin B1 contaminated feed on the performance of broilers

The forty-two days long experiment was conducted on a total of 1000 Arbor Acres broilers, divided into two groups. Both groups of broilers were fed with a commercial feed mixture which consisted of standard feedstuffs and contained enough nutrients regarding the requirements. During the first three weeks of the trial, corn naturally contaminated with AFB₁ 0.0445 ppm per kg dry matter was used in the amount of 20% in the experimental group, while AFB₁ free corn was given to birds in the control group. After the period of toxin administration until the end of the trial, broilers from both groups were normally fed another 5 weeks with uncontaminated feed. In the first phase of the trial, broilers in the control groups had an average daily gain (ADG) of 31 g, average daily feed intake (ADFI) of 45 g and a feed: gain ratio (FCR) of 1.42. In the same time, experimental broilers achieved an ADG of 25 g, ADFI of 35 g and a FCR of 1.39. During the whole period of the trial, control and experimental broilers achieved 49.12 g, 95.24 g and 1.94 and 39.71 g, 86.90 g and 2.19, respectively.     

Mammalian biochronology of the Paleogene-Neogene boundary at Aktau Mountain, eastern Kazakhstan

At Aktau Mountain in the Ili depression of eastern Kazakstan, fossil mammals that encompass the Paleogene-Neogene boundary occur at three stratigraphic levels. The lowest level is in the lower Kyzylbulak Formation and produces Brontotheriidae and the hyracodontidArdynia and is tentatively assigned a late Eocene (Ergilian) age. The lower part of the overlying Aktau Formation produces fossils of the giant rhinocerosParaceratherium and is tentatively assigned a late Oligocene (Tabenbulukian) age. The upper part of the Aktau Formation yields a fossil mammal assemblage that includesGomphotherium,Stephanocemas, Brachypotherium andLagomeryx. It is clearly of Miocene age, probably late early Miocene (late Burdigalian), a correlative of European Reference Level MN 5 and the late Shanwangian of China. The Paleogene-Neogene boundary at Aktau Mountain thus is in the Aktau Formation.     

The spread of somatosensory-evoked potentials within the nervous system

Four thalamic and cortical recordings were carried out in 5 patients. The thalamic-evoked potentials were typical and revealed a triphasic complex, but their latencies showed a relatively high standard deviation. They could be divided into two groups according to their latencies, both of which had low SD. These data suggested that there could be two types of latency of thalamic SEP, because the 4 patients' body sizes were very similar. More detailed surface, cortical and depth recordings are needed to resolve these questions.