Miracle-dz/UniFAR-FTUs huggingface dataset:
Adaptive walks on high-dimensional fitness landscapes and seascapes with distance-dependent statistics

The dynamics of evolution is intimately shaped by epistasis — interactions between genetic elements which cause the fitness-effect of combinations of mutations to be non-additive. Analyzing evolutionary dynamics that involves large numbers of epistatic mutations is intrinsically difficult. A crucial feature is that the fitness landscape in the vicinity of the current genome depends on the evolutionary history. A key step is thus developing models that enable study of the effects of past evolution on future evolution. In this work, we introduce a broad class of high-dimensional random fitness landscapes for which the correlations between fitnesses of genomes are a general function of genetic distance. Their Gaussian character allows for tractable computational as well as analytic understanding. We study the properties of these landscapes focusing on the simplest evolutionary process: random adaptive (uphill) walks. Conventional measures of “ruggedness” are shown to not much affect such adaptive walks. Instead, the long-distance statistics of epistasis cause all properties to be highly conditional on past evolution, determining the statistics of the local landscape (the distribution of fitness-effects of available mutations and combinations of these), as well as the global geometry of evolutionary trajectories. In order to further explore the effects of conditioning on past evolution, we model the effects of slowly changing environments. At long times, such fitness “seascapes” cause a statistical steady state with highly intermittent evolutionary dynamics: populations undergo bursts of rapid adaptation, interspersed with periods in which adaptive mutations are rare and the population waits for more new directions to be opened up by changes in the environment. Finally, we discuss prospects for studying more complex evolutionary dynamics and on broader classes of high-dimensional landscapes and seascapes.
In Vitro and In Vivo Activity of Zabofloxacin and Other Fluoroquinolones Against MRSA Isolates from A University Hospital in Egypt

Abstract The widespread of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), has necessitated the search for alternative therapies; introduction of new agents being a suggestion. This study compares the in vitro and in vivo activities of zabofloxacin, a novel fluoroquinolone, with moxifloxacin, levofloxacin and ciprofloxacin against clinical isolates of MRSA from patients hospitalized in the Alexandria Main University hospital; a tertiary hospital in Alexandria, Egypt, where zabofloxacin has not been yet introduced. The strains tested showed the highest percentage of susceptibility to zabofloxacin (61.2%) among the tested fluoroquinolones with the most effective MIC50 and MIC90 (0.25 and 2 µg/ml, respectively). Time-kill curve analysis revealed a rapid bactericidal activity of zabofloxacin after 6 h of incubation with a quinolone-resistant isolate and complete killing when tested against a quinolone-sensitive isolate with inhibition of regrowth in both cases. PCR amplification and sequencing of QRDRs in selected strains revealed the following amino acid substitutions: Ser-84→Leu in GyrA, Ser-80→Phe in GrlA and Pro-451→Ser in GrlB. The in vivo studies demonstrated that zabofloxacin possessed the most potent protective effect against systemic infection in mice (ED50: 29.05 mg/kg) with lowest count in the dissected lungs (3.66 log10 CFU/ml). The histopathological examination of lung specimens of mice treated with zabofloxacin displayed least congestion, inflammation, oedema and necrosis with clear alveolar spaces and normal vessels. In conclusion, zabofloxacin was proved to possess high in vitro and in vivo efficacy encompassing its comparators and could be considered as a possible candidate for the treatment of infections caused by MRSA. To our knowledge, this is the first study evaluating the in vitro and in vivo activity of zabofloxacin against Egyptian MRSA clinical isolates.
Effect of dietary tryptophan levels on growth and hemato-immunological parameters in juvenile Nile tilapia Oreochromis niloticus.

An 8-week feeding trial was conducted to evaluate the effects of dietary tryptophan on growth performance, feed utilization, hematological parameters and non-specific immune responses of juvenile Nile tilapia. Six isonitrogenous and isoenergetic diets were formulated to contain graded levels of Ltryptophan (0.102%, 0.171%, 0.223%, 0.284%, 0.331% and 0.391% of dry weight respectively) from dietary ingredients and crystalline tryptophan. Each diet was randomly assigned to triplicate groups of 25 juvenile fish (1.41±0.01g) three times daily (8:30, 12:30, and 17:00 hours) to apparent satiation. Results showed that weight gain (WG) and special growth rate (SGR) increased with increased dietary tryptophan levels up to 0.284% and remained nearly the same thereafter. Dietary tryptophan requirement was best expressed by the quadratic regression equation y=6251x+3525x+538.1 R2= 0.895; based on weight gain against dietary tryptophan levels, with optimal dietary tryptophan requirement estimated to be 0.282% of the diet; corresponding to 6.24% of dietary protein on a dry weight basis. Tryptophan supplementation had no impact on the survival rate, body composition, antioxidant activities, hematological parameters, and nonspecific immune parameters of tilapia. Our study indicated that tryptophan supplementation enhanced growth and promoted normal physiology. Our findings could be useful in the aquaculture industry. Published as an open-access journal by the Society of Israeli Aquaculture & Marine Biotechnology (SIAMB). To read papers free of charge, please register online at: http://www.aquaculturehub. org/group/israelijournalofaquaculturebamidgehija The sale of IJA papers is strictly forbidden
Is there anybody out there? Occupancy of the carnivore guild in a temperate archipelago

Carnivores are important components of ecological communities with wide-ranging effects that vary with carnivore size, natural history, and hunting tactics. Researchers and managers should strive to understand both the presence and distribution of carnivores within their local environment. We studied the carnivore guild in the Apostle Islands, where the distribution and occupancy of carnivores was largely unknown. We monitored 19 islands with 160 functioning camera traps from 2014-2017, from which we collected 203,385 photographs across 49,280 trap nights. We documented 7,291 total wildlife events with 1,970 carnivore events, and detected 10 of the 12 terrestrial carnivores found in Wisconsin. Detection rates for species were generally higher in summer than winter, except for coyotes (Canis latrans) and red foxes (Vulpes vulpes). Finitesample occupancy estimates for carnivores varied across islands, with mean estimated occupancy across islands varying from a high of 0.73 for black bears to a low of 0.21 f.
Evidence for Nonesterified Fatty Acids as Modulators of Neutral Lipid Transfers in Normolipidemic Human Plasma

Abstract The relations between the level of plasma nonesterified fatty acid (NEFA) and both the mass concentration and activity of the cholesteryl ester transfer protein (CETP) were studied in fasted normolipidemic subjects. Plasma NEFA correlated positively with both CETP mass concentration (r=.50; P<.01) and the transfer of cholesteryl ester from HDL toward plasma VLDL+LDL (CETHDL→VLDL+LDL activity) (r=.46; P<.05) but not with the transfer of cholesteryl ester from LDL toward plasma HDL (CETLDL→HDL activity) (r=−.05; NS). The high binding capacity of albumin for NEFA was used to investigate whether lipoprotein-bound NEFAs were implicated in the modulation of the cholesteryl ester transfer reaction. As compared with nonsupplemented controls, the addition of an excess of fatty acid–free albumin (8 g/L) to total normolipidemic plasmas reduced CETHDL→VLDL+LDL activity (18.3±5.5% versus 9.8±3.1%; P<.0001) but not CETLDL→HDL activity (22.3±4.5% versus 23.3±5.1%; NS). Moreover, CETHDL→VLDL+LDL and CETLDL→HDL a.
An extensive review of experimental ochratoxicosis in poultry: I. Growth and production parameters along with histopathological alterations

The presence of certain mycotoxins within poultry feed has a negative impact upon the growth and the quality of the final product in the form of meat and eggs. More than 300 different chemically diverse mycotoxins have been identified, but ochratoxins and aflatoxins are considered to be most harmful to the poultry industry. Ochratoxin, more importantly ochratoxin A (OTA) is produced by different species of Aspergillus and Penicillium spp. which are present as storage fungi within the stored grains and feed ingredients. Body weight gain has been found to decrease in a dose dependent manner when infected at rates of 0.5-29.4 mg/kg for 7-60 days in different experimental studies. Decreased feed intake has been observed at levels of 0.5-4 mg/kg OTA fed for 21-60 days, while egg production, hatchability, eggshell thickness and egg mass production is severely affected when 0.5-4 mg/kg OTA in feed was fed for 28-84 days. However, 0.5-20 mg/kg OTA given for between two and 10 weeks of age was sufficient to produce histopathological alterations in the liver, kidney, thymus, bursa of Fabricius, spleen, lungs and heart. The research shows that OTA adversely affects every organ in birds and, in the following review, OTA associated alterations in growth parameters, production performance and histopathological disturbances of different body organs are discussed.
Biocontrol of Diamondback Moth Larvae Tolerant to Bt-toxin Dipel® by the Entomopathogenic Fungus Metarhizium anisopliae (Metschn.) Sorokin (Hypocreales, Ascomycota)

Diamondback moth Plutella xtlostella (Plutellidae, Lepidoptera) is a destructive insect on plants of family Cruciferae. Bacillus thuringiensis toxins, abbreviated Bt-toxins, are biopesticides that could be used for control of larvae of lepidopterous insects. The efficacy of these biopesticides usually decreases due to the development of tolerance to these pesticides by the treated insects. However, this decrease could be compensated by applying biocontrol agents such as entomopathogenic fungi. The objective of the present research was to test the efficacy of Metarhizium anisopliae, as an entomopathogenic fungus, against susceptible and tolerant populations of P. xylostella larvae to Bt-toxin Dipel®. For this purpose, a series of fungus concentrations were used against susceptible and tolerant populations of P. xylostella larvae to Dipel®. Results indicated that there were significant differences (at P=0.05) between the concentrations of M. anisopliae that were used for the treatment of Bt-tolerant and susceptible larvae of P. xylostella. The biocontrol efficacy of M. anisopliae was higher in the susceptible larvae than that in the Bt-tolerant larvae at the concentrations that exceeded 1x10^6 conidia/ml. Probit analysis indicated that the LC50 of the fungus concentrations used for the treatment was 7.70x10^6 conidia/ml for the Bt-tolerant larvae vs. 1.34x10^5 conidia/ml for the susceptible larvae. In conclusion, in spite of the development of low value cross-tolerance in Bt-tolerant P. xylostella larvae to M. anisopliae treatment, there is a good possibility for including this fungus in the integrated control of the insect when develops tolerance to Bt-toxin Dipel® because of high biocontrol efficacy of the fungus.
Oral Microbiota and Cancer Development

Oral microbiota are among the most diverse in the human body. More than 700 species have been identified in the mouth, and new sequencing methods are allowing us to discover even more species. The anatomy of the oral cavity is different from that of other body sites. The oral cavity has mucosal surfaces (the tongue, the buccal mucosa, the gingiva, and the palate), hard tissues (the teeth), and exocrine gland tissue (major and minor salivary glands), all of which present unique features for microbiota composition. The connection between oral microbiota and diseases of the human body has been under intensive research in the past years. Furthermore, oral microbiota have been associated with cancer development. Patients suffering from periodontitis, a common advanced gingival disease caused by bacterial dysbiosis, have a 2–5 times higher risk of acquiring any cancer compared to healthy individuals. Some oral taxa, especially Porphyromonas gingivalis and Fusobacterium nucleatum, have been shown to have carcinogenic potential by several different mechanisms. They can inhibit apoptosis, activate cell proliferation, promote cellular invasion, induce chronic inflammation, and directly produce carcinogens. These microbiota changes can already be seen with potentially malignant lesions of the oral cavity. The causal relationship between microbiota and cancer is complex. It is difficult to accurately study the impact of specific bacteria on carcinoma development in humans. This review focuses on the elucidating the interactions between oral cavity bacterial microbiota and cancer. We gather literature on the current knowledge of the bacterial contribution to cancer development and the mechanisms behind it.
Selection of GmSWEET39 for oil and protein improvement in soybean

Soybean [Glycine max (L.) Merr. ] was domesticated from wild soybean (G. soja Sieb. and Zucc.) and has been further improved as a dual-use seed crop to provide highly valuable oil and protein for food, feed, and industrial applications. However, the underlying genetic and molecular basis remains less understood. Having combined high-confidence bi-parental linkage mapping with high-resolution association analysis based on 631 whole sequenced genomes, we mapped major soybean protein and oil QTLs on chromosome15 to a sugar transporter gene (GmSWEET39). A two-nucleotide CC deletion truncating C-terminus of GmSWEET39 was strongly associated with high seed oil and low seed protein, suggesting its pleiotropic effect on protein and oil content. GmSWEET39 was predominantly expressed in parenchyma and integument of the seed coat, and likely regulates oil and protein accumulation by affecting sugar delivery from maternal seed coat to the filial embryo. We demonstrated that GmSWEET39 has a dual function for both oil and protein improvement and undergoes two different paths of artificial selection. A CC deletion (CC-) haplotype H1 has been intensively selected during domestication and extensively used in soybean improvement worldwide. H1 is fixed in North American soybean cultivars. The protein-favored (CC+) haplotype H3 still undergoes ongoing selection, reflecting its sustainable role for soybean protein improvement. The comprehensive knowledge on the molecular basis underlying the major QTL and GmSWEET39 haplotypes associated with soybean improvement would be valuable to design new strategies for soybean seed quality improvement using molecular breeding and biotechnological approaches.
The Investigation of Relationship Between Annexin A1 Gene Expression and Inflammation in Colorectal Cancer Patients

INTRODUCTION: Annexin A1 (AnxA1) is a protein that inhibits the inflammatory response and is expressed by various types of cells and tissues. Colorectal cancer, a very common type of cancer today, is accompanied by the development of inflammation. At present study, it has been aimed to evaluate the relationship between AnxA1 protein and the development of inflammation in colorectal cancer. METHODS: The study was conducted with 74 colorectal cancer patients and 79 healthy patients as the control group. Serum and RNA were isolated from the blood samples collected from volunteers. AnxA1 and interleukin6 (IL-6) levels in circulation as well as the activity of cytosolic and secretory phospholipase A2 (cPLA2, sPLA2) were determined using Elisa method. AnxA1 and PLA2 mRNA expression levels were measured by real-time PCR technique. RESULTS: While serum AnxA1 levels were significantly decreased in patients group, IL-6 and sPLA2 levels were detected to be increased. AnxA1 mRNA expression was also significantly reduced compared to the control group. The decrease in AnxA1 level was found to correlate with the increase in inflammation markers. DISCUSSION and CONCLUSION: The present study has shown significant changes on AnxA1 plasma protein levels and mRNA expression in colorectal cancer patients. The data have revealed that AnxA1 protein may be associated with inflammation in colorectal cancer. Further studies are needed to elucidate the mechanism of dysregulation in the Annexin protein system.
Hydroxyurea: a reappraisal of its cutaneous side effects and their management

Hydroxyurea (HU) is known to cause a broad spectrum of cutaneous side effects, ranging from relatively benign to severe. Although dermatologists are often consulted for the treatment of these side effects, a comprehensive resource discussing the different types and their management is lacking. In this study, we conducted a literature search in order to critically evaluate the reported types and management of hydroxyurea's cutaneous side effects, as well as review its mechanism of action, dermatologic uses, and common systemic side effects. Relatively common and benign side effects include hyperpigmentation, xerosis, and skin atrophy. While serious cutaneous side effects such as leg ulcers or nonmelanoma skin cancers occur in a substantial proportion of patients, these may resolve with HU discontinuation and proper dermatologic management. Therefore, it is crucial for dermatologists to be aware of these various cutaneous side effects and their management as prompt diagnosis and proper treatment will improve patient outcomes.
Stimulation of Soluble Guanylate Cyclase Diminishes Intrauterine Growth Restriction in a Rat Model of Placental Ischemia.

Placental ischemia in preeclampsia (PE) results in hypertension and intrauterine growth restriction (IUGR). Stimulation of soluble guanylate cyclase (sGC) reduces blood pressure in the clinically relevant reduced uterine perfusion pressure (RUPP) rat model of PE implicating involvement in RUPP-induced hypertension. However, the contribution of sGC in the development of IUGR in PE is not known. Thus, this study demonstrated the efficacy of Riociguat, a sGC stimulator, in IUGR reversion in the RUPP rat model of PE, and tested the hypothesis that improvement in fetal weight occurs in association with improvement in placental perfusion, placental morphology, and placental nutrient transport protein expression. Sham or RUPP surgery was performed at gestational day 14 (G14) with administration of vehicle (Sham or RUPP) or the sGC stimulator (Riociguat, 10mg/kg/day, s.c.) (sGC-treated) until G20. Fetal weight was reduced (p=0.004) at G20 in RUPP but not sGC-treated RUPP compared to Sham, the control group. At G20, uterine artery resistance index (UARI) was increased (p=0.010) in RUPP indicating poor placental perfusion; proportional junctional zone surface area was elevated (p=0.035) indicating impaired placental development. These effects were ameliorated in sGC-treated RUPP. Placental protein expression of nutrient transporter heart fatty acid binding protein (hFABP) was increased (p=0.008) in RUPP but not sGC-treated RUPP suggesting a compensatory mechanism to maintain normal neurodevelopment. Yet, UARI (p<0.001), proportional junctional zone surface area (p=0.013), and placental hFABP protein expression (p=0.008) were increased in sGC-treated Sham suggesting a potential adverse effect of Riociguat. Collectively, these results suggest sGC contributes to IUGR in PE.
Therapeutic implications of dermoscopic findings in acanthosis nigricans: A clinical and histopathological study

Acanthosis nigricans is associated with numerous systemic disorders. These include endocrinological conditions such as, diabetes, acromegaly, Cushing's syndrome, thyroid dysfunction, as well as metabolic abnormalities like obesity and polycystic ovarian disease. Its association with visceral malignancy is known. Moreover, Acanthosis nigricans is known to be a cutaneous marker of insulin resistance (IR) and hyperinsulinemia. The primary aim of this study was to study clinical and histopathological patterns of acanthosis nigricans and its correlation with dermoscopic patterns and treatment implications. 103 patients clinically diagnosed as acanthosis nigricans were enrolled in the study. Clinical evaluation, dermoscopy, and skin biopsy was done for histopathological evaluation. Consistency was observed in the changes seen on dermoscopy with clinical and histopathological findings. Common dermoscopy findings were Crista Cutis, Sulcus Cutis, Papillary projections, hyperpigmented dots, crypts, and blotching Dermoscopic findings can be correlated with histopathological features. Dermoscopy allows visualization on higher magnification which helps to pick up subtle changes which are not visible to naked eye. Dermoscopy can be a useful tool to distinguish acanthosis nigricans from other pigmentary disorders in patients who are not willing for histopathological examination and helps in treatment making decisions.
Intracellular escape strategies of Staphylococcus aureus in persistent cutaneous infections

Pathogenic invasion of Staphylococcus aureus is a major concern in patients with chronic skin diseases like atopic dermatitis (AD), epidermolysis bullosa (EB), or chronic diabetic foot and venous leg ulcers, and can result in persistent and life‐threatening chronic non‐healing wounds. Staphylococcus aureus is generally recognized as extracellular pathogens. However, S. aureus can also invade, hide and persist in skin cells to contribute to wound chronicity. The intracellular life cycle of S. aureus is currently incompletely understood, although published studies indicate that its intracellular escape strategies play an important role in persistent cutaneous infections. This review provides current scientific knowledge about the intracellular life cycle of S. aureus in skin cells, which can be classified into professional and non‐professional antigen‐presenting cells, and its strategies to escape adaptive defense mechanisms. First, we discuss phenotypic switch of S. aureus, which affects intracellular routing and degradation. This review also evaluates potential intracellular escape mechanism of S. aureus to avoid intracellular degradation and antigen presentation, preventing an immune response. Furthermore, we discuss potential drug targets that can interfere with the intracellular life cycle of S. aureus. Taken together, this review aimed to increase scientific understanding about the intracellular life cycle of S. aureus into skin cells and its strategies to evade the host immune response, information that is crucial to reduce pathogenic invasion and life‐threatening persistence of S. aureus in chronic cutaneous infections.