Biology

The tumor microenvironment is a complex network of various interactions between immune cells and non-cellular components such as the extracellular matrix, exosomes and interleukins. Moreover, tumor heterogeneity and its constant modification may alter the immunophenotype and become responsible for its resistance regarding the therapies applied However, it should be remembered that in a strongly immunosuppressive neoplastic microenvironment, the immune system cells undergo reprogramming and most often cease to fulfill their original function. Therefore, understanding what happens within the tumor microenvironment, and which mechanisms are responsible for tumor development and progression should let us know how cancer could protect itself against the immune system. The presented review summarizes the latest information on the interactions between the tumor microenvironment and the cellular and non-cellular components, as well as their impact on cancer development, progression and immune system exhaustion. Full article

Controlling the activity of the heterohexameric Mcm2–7 replicative helicase is crucial for regulation of replication origin activity in eukaryotes. Because bidirectional replication forks are generated from every replication origin, when origins are licensed for replication in the first step of DNA replication, two inactive Mcm2–7 heterohexiameric complexes are loaded around double stranded DNA as a head-to-head double hexamer. The helicases are subsequently activated via a ‘firing’ reaction, in which the Mcm2–7 double hexamer is converted into two active helicase units, the CMG complex, by firing factors. Dimerization of firing factors may contribute to this process by allowing simultaneous activation of two sets of helicases and thus efficient assembly of bidirectional replication forks. An example of this is dimerization of the firing factor Sld3/Treslin/Ticrr via its binding partner, Sld7/MTBP. In organisms in which no Sld7 ortholog has been identified, such as the fission yeast Schizosaccharomyces pombe, Sld3 itself has a dimerization domain, and it has been suggested that this self-interaction is crucial for the firing reaction in this organism. Dimerization induces a conformational change in Sdl3 that appears to be critical for the firing reaction. Moreover, Mcm10 also seems to be regulated by self-interaction in yeasts. Although it is not yet clear to what extent dimerization of firing factors contributes to the firing reaction in eukaryotes, we discuss the possible roles of firing factor dimerization in simultaneous helicase activation. Full article

Degradation products of herbicides, alone and in combination, may affect non-target aquatic organisms via leaching or runoff from the soil. The effects of 50-day exposure of primary metabolites of chloroacetamide herbicide, acetochlor ESA (AE; 4 µg/L), and glyphosate, aminomethylphosphonic acid (AMPA; 4 µg/L), and their combination (AMPA + AE; 4 + 4 µg/L) on mortality, growth, oxidative stress, antioxidant response, behaviour, and gill histology of early life stages of marbled crayfish (Procambarus virginalis) were investigated. While no treatment effects were observed on cumulative mortality or early ontogeny, growth was significantly lower in all exposed groups compared with the control group. Significant superoxide dismutase activity was observed in exposure groups, and significantly higher glutathione S-transferase activity only in the AMPA + AE group. The gill epithelium in AMPA + AE-exposed crayfish showed swelling as well as numerous unidentified fragments in interlamellar space. Velocity and distance moved in crayfish exposed to metabolites did not differ from controls, but increased activity was observed in the AMPA and AE groups. The study reveals the potential risks of glyphosate and acetochlor herbicide usage through their primary metabolites in the early life stages of marbled crayfish. Full article

Gilaburu (Viburnum opulus L.) is an important fruit that has been studied in recent years due to its phytochemicals and health benefits. In this study, traditionally produced vinegar made from gilaburu fruit (C-GV) was evaluated. Vinegar with higher levels of bioactive components optimized by response surface methodology (RSM) was also produced using ultrasound (UT-GV). The maximum optimization result for the bioactive components was achieved at 14 min and 61.2 amplitude. The effectiveness of thermal pasteurization (P-GV) on gilaburu vinegar was evaluated. An increase was detected for every organic acid with ultrasound treatment. In the UT-GV and C-GV samples, arabinose was present, which is useful for stimulating the immune system. Gilaburu vinegar samples contained 29–31 volatile compounds. The smallest amount of volatile compounds was found in P-GV (1280.9 µg/kg), and the largest amounts of volatile compounds were found in C-GV (1566.9 µg/kg) and UT-GV (1244.10 µg/kg). In the UT-GV sample, Fe was increased, but Ca, K, Mg, and Mn were decreased. A total of 15 polyphenols were detected in C-GV, P-GV, and UT-GV samples, and gallic acid was the most common. A total of 17 free amino acids were detected in gilaburu vinegar samples. Ultrasound provided enrichment in total phenolic compounds and total free amino acids. All three vinegar samples had good antimicrobial activity against pathogens. The efficacy of C-GV, P-GV, and UT-GV samples against colon and stomach cancer was determined, but there were no significant differences between them. As a result, ultrasound treatment is notable due to its antimicrobial and anticancer activity, especially for the enrichment of phenolic compounds and amino acids in gilaburu vinegar. Full article

The purpose of this systematic review and meta-analysis was to qualitatively synthesize and quantitatively assess the evidence of the relationship between objectively determined volumes of physical activity (PA) and cardiometabolic health in women. Four databases (PubMed, Web of Science, Scopus, and the Cochrane library) were searched and, finally, 24 eligible studies were included, with a total of 2105 women from eight countries. A correlational meta-analysis shows that moderate-to-vigorous intensity physical activity (MVPA) was favorably associated with high-density lipoprotein (r = 0.16; 95% CI: 0.06, 0.25; p = 0.002); however, there was limited evidence for the effects of most of the other cardiometabolic biomarkers recorded from steps, total physical activity, light- and moderate-intensity physical activity and MVPA. It is most compelling and consistent that being more physically active is beneficial to the metabolic syndrome. Overall, PA levels are low in adult women, suggesting that increasing the total volume of PA is more important than emphasizing the intensity and duration of PA. The findings also indicate that, according to the confounding effects of body composition and cardiorespiratory fitness, meeting the minimal level of 150 min of moderate-intensity physical activity recommended is not enough to obtain a significant improvement in cardiometabolic indicators. Nonetheless, the high heterogeneity between studies inhibits robust conclusions. Full article

Low back pain (LBP) is a globally prevalent and costly societal problem with multifactorial etiologies and incompletely understood pathophysiological mechanisms. To address such shortcomings regarding the role of neurotrophins in the underlying mechanisms of pain, an LBP model was developed in rats involving two unilateral intramuscular injections of nerve growth factor (NGF) into deep trunk muscles. To date, behavioral investigations of this NGF-LBP model have been limited, especially as it pertains to female pain behaviors. This study compared mechanical sensitivity to noxious (hyperalgesia) and non-noxious (hypersensitivity) stimuli in control and NGF-injected male and female rats through pain resolution. Although the baseline testing revealed no differences between males and females, NGF-injected females demonstrated prolonged ipsilateral deep trunk mechanical hyperalgesia that resolved seven days later than males. Moreover, females showed bilateral trunk mechanical sensitivity to noxious and non-noxious stimuli compared to only ipsilateral behaviors in males. Sex differences were also observed in the severity of behavioral responses, with females displaying greater mean differences from baseline at several timepoints. Overall, these NGF-LBP behavioral findings mirror some of the sex differences reported in the clinical presentation of LBP and accentuate the translatability of this NGF-LBP model. Future studies using this LBP-NGF model could help to elucidate the neurobiological mechanisms responsible for the development, severity, and/or resolution of muscular LBP as well as to provide insights into the processes governing the transition from acute to chronic LBP. Full article

Posidonia oceanica meadows are Mediterranean coastal habitats of great conservation importance. This study is focused on a meadow located at Tremiti Islands Marine Protected Area (Adriatic Sea, Italy), which was monitored in 2003, 2015, and 2020 to evaluate its health state over time in relation to coastal human activities, which have been highly affecting this MPA for the last 20 years. To assess any change in the physiognomy of the meadow, rhizome density, percentage coverage, and lower limit progressions and/or regression over time were evaluated by scuba diving, while the distribution and extension of the meadow were assessed through habitat mapping using a side-scan sonar. Moreover, phenological and lepidochronological analyses were performed on the collected rhizomes to assess the leaf area index (LAI, m²m⁻²) and the rhizome age (lepidochronological years). Our study showed a general deterioration of P. oceanica meadow from 2003 to 2020, with a significant reduction of its absolute and relative rhizome density and LAI at almost all sampling stations, absence of renovation of the meadow, and lower limit regression and overall worsening of the main conservation status indicators. However, appropriate management actions, such as the establishment of mooring buoy fields, supported the improvement of the P. oceanica status at the local scale with a significant increase in density and LAI and the presence of active stolonization processes, suggesting that mitigation actions can play a crucial role in the conservation of this habitat. On the contrary, local anthropogenic impacts, especially anchoring and coastal development, markedly affect the resilience of P. oceanica meadows to global stressors, such as climate change. Full article

Intensive agriculture is essential to feed increasing populations, yet requires large amounts of pesticide, fertiliser, and water to maintain productivity. One solution to mitigate these issues is the adoption of Vertical Farming Systems (VFS). The self-contained operation of these facilities offers the potential to recycle agricultural inputs, as well as sheltering crops from the effects of climate change. Recent technological advancements in light-emitting diode (LED) lighting technology have enabled VFS to become a commercial reality, although high electrical consumption continues to tarnish the environmental credentials of the industry. In this review, we examine how the inherent use of electricity by VFS can be leveraged to deliver commercial and environmental benefits. We propose that an understanding of plant photobiology can be used to vary VFS energy consumption in coordination with electrical availability from the grid, facilitating demand-side management of energy supplies and promoting crop yield. Full article

The data of this study revealed that Tigger was found in a wide variety of animal genomes, including 180 species from 36 orders of invertebrates and 145 species from 29 orders of vertebrates. An extensive invasion of Tigger was observed in mammals, with a high copy number. Almost 61% of those species contain more than 50 copies of Tigger; however, 46% harbor intact Tigger elements, although the number of these intact elements is very low. Common HT events of Tigger elements were discovered across different lineages of animals, including mammals, that may have led to their widespread distribution, whereas Helogale parvula and arthropods may have aided Tigger HT incidences. The activity of Tigger seems to be low in the kingdom of animals, most copies were truncated in the mammal genomes and lost their transposition activity, and Tigger transposons only display signs of recent and current activities in a few species of animals. The findings suggest that the Tigger family is important in structuring mammal genomes. Full article

The mammalian tongue plays a fundamental role in various physiological and behavioral activities. Significant morphological variations have been recorded in the tongue of several species. This study aims to obtain detailed histological and morphometric information about the filiform papillae on the surface of rat tongue. The tongues of five 10-month-old Wistar rats were utilized, which were later examined with a stereo-microscope. Fragments from the three regions of the tongue were collected for histological investigations. The tongue of the Wistar rat has an intensely keratinized stratified squamous epithelium, with the highest degree of keratinized epithelium covering the filiform papillae. The filiform papillae differ in density, with the highest density recorded on the posterior part of the lingual body and the lowest density on the protuberance. The shortest filiform papillae were observed on the apex of the tongue and the tallest on the anterior part of the lingual body. Interestingly, the orientation of the filiform papillae on the lingual protuberance was inclined posteroanteriorly, in the opposite way as compared to the papillae from all the other regions of the tongue. Histologically, a difference was recorded in the structure of the covering epithelium of the anterior vs. the posterior face of the filiform papillae. Full article

Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS. Full article

Clubroot disease, caused by Plasmodiophora brassicae, is a serious threat to Chinese cabbage (Brassica rapa subsp. pekinensis) production, which results in extensive yield losses. At present, clubroot control mainly depends upon pesticides, which provoke food-safety concerns, and the application of sole biocontrol agents cannot successfully control the disease. In this study, we investigated the effect of Bacillus cereus BT-23, Lysobacter antibioticus 13-6, and Lysobacter capsici ZST1-2 as sole strains, intra-/inter-genus co-culture, and microbial consortia on clubroot disease, plant growth, and rhizosphere bacterial diversity in a field experiment. The microbial consortia efficiently controlled the incidence of clubroot disease, with a biocontrol effect of about 65.78%, by decreasing the soil acidity and enhancing the yield (17,662.49 kg/acre). The high-throughput sequencing results demonstrated that the phyla Proteobacteria and Bacteroidetes were present in high relative abundance in the rhizosphere soil of the Chinese cabbage. Furthermore, Firmicutes was found as a unique phylum in the rhizosphere soil of CK-H and T1-T7, except for CK-D. The application of microbial consortia recovers the imbalance in indigenous microbial communities. Therefore, we conclude that microbial consortia can reduce the clubroot incidence in Chinese cabbage by decreasing the soil acidity and altering the diversity and structure of rhizosphere bacterial communities. This study highlights the potential of microbial consortia as an engineering tool to control devastating soilborne diseases in commercial crops. Full article

The adjusted binary classification (ABC) approach was proposed to assure that the binary classification model reaches a particular accuracy level. The present study evaluated the ABC for osteometric sex classification using multiple machine learning (ML) techniques: linear discriminant analysis (LDA), boosted generalized linear model (GLMB), support vector machine (SVM), and logistic regression (LR). We used 13 femoral measurements of 300 individuals from a modern Turkish population sample and split data into two sets: training (n = 240) and testing (n = 60). Then, the five best-performing measurements were selected for training univariate models, while pools of these variables were used for the multivariable models. ML classifier type did not affect the performance of unadjusted models. The accuracy of univariate models was 82–87%, while that of multivariate models was 89–90%. After applying ABC to the crossvalidation set, the accuracy and the positive and negative predictive values for uni- and multivariate models were ≥95%. Sex could be estimated for 28–75% of individuals using univariate models but with an obvious sexing bias, likely caused by different degrees of sexual dimorphism and between-group overlap. However, using multivariate models, we minimized the bias and properly classified 81–87% of individuals. A similar performance was also noted in the testing sample (except for FEB), with accuracies of 96–100%, and a proportion of classified individuals between 30% and 82% in univariate models, and between 90% and 91% in multivariate models. When considering different training sample sizes, we demonstrated that LR was the most sensitive with limited sample sizes (n < 150), while GLMB was the most stable classifier. Full article

The prognostic significance of the length of internal tandem duplication (ITD) insertions in mutant FLT3 genes in acute myeloid leukemia (AML) is controversial. We conducted a retrospective study to evaluate the correlation between the ITD base-pair (bp) insertion length and clinical outcomes. The mutational status of the FLT3 gene was evaluated in 402 of 467 consecutive AML patients treated at the University of Maryland Greenebaum Comprehensive Cancer Center between 2013 and 2020; 77 had FLT3-ITD mutations. Patients were divided into three cohorts based on bp insertion length (<30 (0–33rd percentile), 30–53 (34th–66th percentile),and >53 (>66th percentile)). The median overall survival (OS) of patients was 16.5 months (confidence interval (CI) 7.3-NA), 18.5 months (CI 7.3-NA), and 21.9 months (CI 19.1-NA) (p = 0.03) for the <30, 30–53, and >53 bp insertion length cohorts, respectively. The adjusted median event-free survival (EFS) for the ITD insertion lengths >30, 30–53, and >53 bp was 11.1 months (CI 2.8–16.5), 5.2 months (CI 2.9–12.6), and 9.1 months (CI 5.4-NA) (p = 0.5), respectively. Complete remission (CR) rates were 64% (<30 inserted bp), 55% (30–53 inserted bp), and 79% (>53 inserted bp) (p = 0.23). For patients treated with gilteritinib and midostaurin, the unadjusted median OS was not statistically significantly different between cohorts. Full article

Climate change alters organismal performance via shifts in temperature. However, we know little about the relative fitness impacts of climate variability and how cold-adapted ectotherms mediate these effects. Here, we advance the field of climate change biology by directly testing for species performance, considering the effects of different thermal environments at the first developmental stage of larvae. We conducted our experiments in climatic chambers (2019–2020) using five cold-adapted butterflies of the genus Erebia (Erebia aethiops, Erebia cassioides, Erebia manto, Erebia tyndarus, Erebia nivalis). Larvae were reared indoors and were treated with higher and lower temperatures than those of their mothers’ origins. Overall, we found evidence of better performance at warmer temperatures and a decreased performance at lower temperatures, and larvae were able to tolerate small temperature changes from mother’s origin. Warmer conditions, however, were unfavorable for E. nivalis, indicative of its limited elevational range and its poor ability to mediate a variety of thermal conditions. Further, larvae generally performed poorly where there was a large difference in thermal regimen from that of their maternal origin. Future efforts should include additional life history stages and focus on a more mechanistic understanding of species thermal tolerance. Such studies could increase the realism of predicted responses to climate change and could account for asynchronous changes in species development, which will alter community composition and ecosystem functioning. Full article

Gaucher disease is a disorder of lysosomes caused by a functional defect of the glucocerebrosidase enzyme. The disease is mainly due to mutations in the GBA1 gene, which determines the gradual storage of glucosylceramide substrate in the patient’s macrophages. In this paper, we describe the case of a 38-year-old man who clinically presented with hyperferritinemia, thrombocytopenia, leukopenia, anemia and mild splenomegaly; a diagnosis of hemochromatosis was made 10 years earlier. Re-evaluation of the clinical case led to a suspicion of Gaucher disease, which was confirmed by enzymatic analysis, which was found to be below the normal range, and genetic evaluation, which identified compound heterozygosity N370S/RecNciI. We know that patients suffering from Gaucher disease can also have high ferritin levels. Even if the mechanism underlying the changes in iron metabolism is not yet elucidated, the chronic mild inflammatory state present in these patients probably causes the storage of ferritin in macrophages, resulting in hyperferritinemia. Therefore, in the presence of few typical signs and symptoms of the disease should raise an alarm bell in the clinicians, inducing clinical suspicion of Gaucher disease. Misdiagnosis and diagnostic delay in metabolic diseases could cause irreversible organ damage and delay the start of specific therapy for these patients. Full article

The main goal of the study was to determine changes in the bacterial structure in bottom sediments occurring over the seasons of the year and to estimate microbial metabolic activity. Bottom sediments were collected four times in the year (spring, summer, autumn, and winter) from 10 different measurement points in Cardinal Pond (Ślesin, NW Poland). The Next-Generation Sequencing (MiSeq Illumina) and Community-Level Physiological Profiling techniques were used for identification of the bacterial diversity structure and bacterial metabolic and functional activities over the four seasons. It was evident that Proteobacteria, Acidobacteria, and Bacteroidetes were the dominant phyla, while representatives of Betaproteobacteria, Gammaproteobacteria, and Deltaproteobacteria predominated at the class level in the bottom sediments. An impact of the season on biodiversity and metabolic activity was revealed with the emphasis that the environmental conditions in summer modified the studied parameters most strongly. Carboxylic and acetic acids and carbohydrates were metabolized most frequently, whereas aerobic respiration I with the use of cytochrome C was the main pathway used by the microbiome of the studied bottom sediments. Full article

Walking at speeds higher than transition speed is associated with a decrease in the plantar-flexor muscle fibres’ ability to produce force and, potentially, to an impaired behaviour of the muscle–tendon unit (MTU) elastic components. This study aimed to investigate the ankle joint functional indexes and the Achilles tendon mechanical behaviour (changes in AT force and power) to better elucidate the mechanical determinants of the walk-to-run transition. Kinematics, kinetic and ultrasound data of the gastrocnemius medialis (GM) were investigated during overground walking and running at speeds ranging from 5–9 km·h⁻¹. AT and GM MTU force and power were calculated during the propulsive phase; the ankle joint function indexes (damper, strut, spring and motor) were obtained using a combination of kinetic and kinematic data. AT force was larger in running at speeds > 6.5 km/h. The contribution of AT to the total power provided by the GM MTU was significantly larger in running at speeds > 7.5 km/h. The spring and strut indexes of the ankle were significantly larger in running at speeds > 7.5 km/h. These data suggest that the walk-to-run transition could (at least partially) be explained by the need to preserve AT mechanical behaviour and the ankle spring function. Full article

C-type natriuretic peptide (CNP) is the third member of the natriuretic peptide family. Unlike other members, i.e., atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are cardiac hormones secreted from the atrium and ventricle of the heart, respectively, CNP is regarded as an autocrine/paracrine regulator with broad expression in the body. Because of its low expression levels compared to ANP and BNP, early studies failed to show its existence and role in the heart. However, recent studies have revealed the physiological and pathophysiological importance of CNP in the heart; in concert with the distribution of its specific natriuretic peptide receptor-B (NPR-B), CNP has come to be regarded as the major heart-protective natriuretic peptide in the failed heart. NPR-B generates intracellular cyclic guanosine 3′,5′-monophosphate (cGMP) upon CNP binding, followed by various molecular effects including the activation of cGMP-dependent protein kinases, which generates diverse cytoprotective actions in cardiomyocytes, as well as in cardiac fibroblasts. CNP exerts negative inotropic and positive lusitropic responses in both normal and failing heart models. Furthermore, osteocrin, the intrinsic and specific ligand for the clearance receptor for natriuretic peptides, can augment the effects of CNP and may supply a novel therapeutic strategy for cardiac protection. Full article