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The interkingdom horizontal gene transfer in 44 early diverging fungi boosted their metabolic, adaptive, and immune capabilities
Get PDFNumerous studies have been devoted to individual cases of horizontally acquired genes in fungi. It has been shown that such genes
expand the hosts’ metabolic capabilities and contribute to their adaptations as parasites or symbionts. Some studies have provided
an extensive characterization of the horizontal gene transfer (HGT) in Dikarya. However, in the early diverging fungi (EDF), a similar
characterization is still missing. In order to fill this gap, we have designed a computational pipeline to obtain a statistical sample of
reliable HGT events with a low false discovery rate. We have analyzed 44 EDF proteomes and identified 829 xenologs in fungi ranging
from Chytridiomycota to Mucoromycota. We have identified several patterns and statistical properties of EDF HGT. We show that HGT
is driven by bursts of gene exchange and duplication, resulting in highly divergent numbers and molecular properties of xenologs
between fungal lineages. Ancestrally aquatic fungi are generally more likely to acquire foreign genetic material than terrestrial ones.
Endosymbiotic bacteria can be a source of useful xenologs, as exemplified by NOD-like receptors transferred to Mortierellomycota.
Closely related fungi have similar rates of intronization of xenologs. Posttransfer gene fusions and losses of protein domains are
common and may influence the encoded proteins’ functions. We argue that there is no universal approach for HGT identification and
inter- and intra-kingdom transfers require tailored identification methods. Our results help to better understand how and to what
extent HGT has shaped the metabolic, adaptive, and immune capabilities of fungi
The strain-dependent cytostatic activity of Lactococcus lactis on CRC cell lines is mediated through the release of arginine deiminase
Get PDFAbstract
Background Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, posing a serious public
health challenge that necessitates the development of new therapeutics, therapies, and prevention methods. Among
the various therapeutic approaches, interventions involving lactic acid bacteria (LAB) as probiotics and postbiotics
have emerged as promising candidates for treating and preventing CRC. While human-isolated LAB strains are
considered highly favorable, those sourced from environmental reservoirs such as dairy and fermented foods are also
being recognized as potential sources for future therapeutics.
Results In this study, we present a novel and therapeutically promising strain, Lactococcus lactis ssp. lactis Lc4,
isolated from dairy sources. Lc4 demonstrated the ability to release the cytostatic agent - arginine deiminase (ADI)
- into the post-cultivation supernatant when cultured under conditions mimicking the human gut environment.
Released arginine deiminase was able to significantly reduce the growth of HT-29 and HCT116 cells due to the
depletion of arginine, which led to decreased levels of c-Myc, reduced phosphorylation of p70-S6 kinase, and cell
cycle arrest. The ADI release and cytostatic properties were strain-dependent, as was evident from comparison to
other L. lactis ssp. lactis strains.
Conclusion For the first time, we unveil the anti-proliferative properties of the L. lactis cell-free supernatant (CFS),
which are independent of bacteriocins or other small molecules. We demonstrate that ADI, derived from a dairy-
Generally Recognized As Safe (GRAS) strain of L. lactis, exhibits anti-proliferative activity on cell lines with different
levels of argininosuccinate synthetase 1 (ASS1) expression. A unique feature of the Lc4 strain is also its capability to
release ADI into the extracellular space. Taken togethe
Fungal Biostarter and Bacterial Occurrence of Dry-Aged Beef: The Sensory Quality and Volatile Aroma Compounds after 21 Days of Aging
Get PDFIn this study, we decided to test the hypothesis that the fungal biostarter M. flavus used during a 21-day beef dry-aging process significantly impacts the composition of other microorganisms, the profile of volatile compounds, meat hardness characteristics, and, consequently, the sensory quality. The experiments were performed on samples derived from animals crossbred between Holstein–Fresian cows and meat breed bulls. Two groups of samples were studied, including the control group, without biostarter, and a group inoculated with the M. flavus biostarter. Both sample groups were seasoned for 21 days in the dry-aging fridge. The physicochemical parameters (pH, color parameters), the chemical composition of muscle, the determination of the shear force, the profile of volatile compounds (VOCs), and the sensory quality were evaluated after aging. During this study, classical microbiological methods were used to investigate the influence of fungal biostarters on the growth and survival of bacteria and other fungi (e.g., yeasts) during the dry-aging process of beef (DAB). The M. flavus biostarter improved the sensory quality of DAB, allowing high sensory quality to be achieved after just 21 days. This is likely due to the diverse VOCs produced by the fungus, including 1-tetradecanol, 2-nonenal, trans-2-undecenoic acid, and the following esters: formic acid hexyl ester, 10-undecenoic acid methyl ester, and 4-methylpentanoic acid methyl ester. The presence of the biostarter had no significant effect on the number of the bacteria or the survivability of the L. monocytogenes on the meat’s surface in laboratory conditions
Phosphorylation of P-stalk proteins defines the ribosomal state for interaction with auxiliary protein factors
Get PDFRibosomal action is facilitated by the orchestrated work of trans-acting factors and ribosomal elements, which are subject to regulatory events, often involving phosphorylation. One such element is the ribosomal P-stalk, which plays a dual function: it activates translational GTPases, which support basic ribosomal functions, and interacts with the Gcn2 kinase, linking the ribosomes to the ISR pathway. We show that P-stalk proteins, which form a pentamer, exist in the cell exclusively in a phosphorylated state at five C-terminal domains (CTDs), ensuring optimal translation (speed and accuracy) and may play a role in the timely regulation of the Gcn2-dependent stress response. Phosphorylation of the CTD induces a structural transition from a collapsed to a coil-like structure, and the CTD gains conformational freedom, allowing specific but transient binding to various protein partners, optimizing the ribosome action. The report reveals a unique feature of the P-stalk proteins, indicating that, unlike most ribosomal proteins, which are regulated by phosphorylation in an on/off manner, the P-stalk proteins exist in a constantly phosphorylated state, which optimizes their interaction with auxiliary factors
Modeling of mRNA deadenylation rates reveal a complex relationship between mRNA deadenylation and decay
Get PDFComplete cytoplasmic polyadenosine tail (polyA-tail) deadenylation
is thought to be essential for initiating mRNA decapping
and subsequent degradation. To investigate this prevalent model,
we conducted direct RNA sequencing of S. cerevisiae mRNAs
derived from chase experiments under steady-state and stress
condition. Subsequently, we developed a numerical model based on
a modified gamma distribution function, which estimated the
transcriptomic deadenylation rate at 10 A/min. A simplified independent
method, based on the delineation of quantile polyA-tail
values, showed a correlation between the decay and deadenylation
rates of individual mRNAs, which appeared consistent within
functional transcript groups and associated with codon optimality.
Notably, these rates varied during the stress response. Detailed analysis of ribosomal protein-coding mRNAs (RPG mRNAs), constituting 40% of the transcriptome, singled out this transcript group. While deadenylation and decay of RPG mRNAs accelerated under heat stress, their degradation could proceed even when deadenylation was blocked, depending entirely on ongoing nuclear export. Our findings support the general primary function of deadenylation in dictating the onset of decapping, while also demonstrating complex relations between these processes
The Effect of Lacticaseibacillus paracasei LPC100 and Lactiplantibacillus plantarum LP140 on Bone Mineral Density in Postmenopausal Women: A Multicenter, Randomized, Placebo-Controlled Study
Get PDFObjectives: modulation of gut microbiota by probiotics has been proposed as a target for intervention to reduce bone mineral density (BMD) loss in the postmenopausal period. This study aims to evaluate the effect of Lacticaseibacillus (L.) paracasei LPC100 and Lactiplantibacillus (L.) plantarum LP140 on BMD in postmenopausal women in a multicenter, randomized, double-blind, placebo-controlled trial. Methods: the primary outcome was the change in T-score of the lumbar spine measured by dual-energy X-ray absorptiometry assessed after twelve-month probiotic supplementation. Secondary outcomes included changes in serological markers of inflammation and calcium–phosphate metabolism, body mass index, gastrointestinal symptoms, and satisfaction with the intervention. Results: a decrease in T-score indicating the progressive bone demineralization reached a statistically significant difference in the placebo group (from mean values of 0.06 ± 1.04 to −0.28 ± 1.12, p = 0.041) but not in the probiotic group (0.19 ± 0.99 and −0.08 ± 1.05, respectively, p = 0.125) with a p-value = 0.089 between the groups. No significant differences were found in secondary outcomes with the exception of vitamin D concentration and a significant reduction in some gastrointestinal symptoms in the probiotic group. A significant decrease in vitamin D level was observed only in the placebo group (p = 0.014). Probiotics were safe and well tolerated. Conclusions: this study suggests that the oral administration of L. paracasei LPC100 and L. plantarum LP140 may be a viable strategy to prevent BMD loss and vitamin D deficiency in postmenopausal women, but further research is necessary to confirm clinical benefits and to know the mechanism of action [ClinicalTrial.gov NCT06375668]
Hollow fiber bioreactor with genetically modified hepatic cells as a model of biologically active function block of the bioartificial liver
Get PDFChronic liver disease and cirrhosis, that can lead to liver failure, are major public health issues, with liver
transplantation as the only effective treatment. However, the limited availability of transplantable organs has
spurred research into alternative therapies, including bioartificial livers. To date, liver hybrid support devices,
using porcine hepatocytes or hepatoma-derived cell lines, have failed to demonstrate efficacy in clinical trials.
Here, for the first time, we report the construction of a model of biologically active function block of bioartificial
liver based on a hollow fiber bioreactor populated with genetically modified hepatic cells. For
comprehensive comparison the culturing of hepatic cells was carried out in both static and dynamic conditions in
a medium that flowed through porous polysulfone capillaries. The most crucial parameters, such as cell viability,
glucose consumption, albumin secretion and urea production, were analyzed in static conditions while glucose
usage and albumin production were compared in dynamic cell cultures. This model has the potential to improve
the development of bioartificial liver devices and contribute to the treatment of patients with impaired liver
function
The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity
Get PDFObesity and chronic low-grade inflammation, often occurring together, significantly contribute to severe metabolic and inflammatory conditions like type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. A key player is elevated levels of gut dysbiosis-associated lipopolysaccharide (LPS), which disrupts metabolic and immune signaling leading to metabolic endotoxemia, while short-chain fatty acids (SCFAs) beneficially regulate these processes during homeostasis. SCFAs not only safeguard the gut barrier but also exert metabolic and immunomodulatory effects via G protein-coupled receptor binding and epigenetic regulation. SCFAs are emerging as potential agents to counteract dysbiosis-induced epigenetic changes, specifically targeting metabolic and inflammatory genes through DNA methylation, histone acetylation, microRNAs
(miRNAs), and long non-coding RNAs (lncRNAs). To assess whether SCFAs can effectively interrupt the detrimental cascade of obesity and inflammation, this review aims to provide a comprehensive overview of the current evidence for
their clinical application. The review emphasizes factors influencing SCFA production, the intricate connections between metabolism, the immune system, and the gut microbiome, and the epigenetic mechanisms regulated by SCFAs that impact metabolism and the immune system
Hypertensive rats show increased renal excretion and decreased tissue concentrations of glycine betaine, a protective osmolyte with diuretic properties
Get PDFHypertension leads to water-electrolyte disturbances and end-organ damage. Betaine is an
osmolyte protecting cells against electrolyte imbalance and osmotic stress, particularly in
the kidneys. This study aimed to evaluate tissue levels and hemodynamic and renal effects
of betaine in normotensive and hypertensive rats. Betaine levels were assessed using highperformance
liquid chromatography-mass spectrometry (HPLC-MS) in normotensive rats
(Wistar-Kyoto, WKYs) and Spontaneously Hypertensive rats (SHRs), a model of genetic
hypertension. Acute effects of IV betaine on blood pressure, heart rate, and minute diuresis
were evaluated. Gene and protein expression of chosen kidney betaine transporters
(SLC6a12 and SLC6a20) were assessed using real-time PCR and Western blot. Compared
to normotensive rats, SHRs showed significantly lower concentration of betaine in blood
serum, the lungs, liver, and renal medulla. These changes were associated with higher urinary
excretion of betaine in SHRs (0.20 ± 0.04 vs. 0.09 ± 0.02 mg/ 24h/ 100g b.w., p =
0.036). In acute experiments, betaine increased diuresis without significantly affecting arterial
blood pressure. The diuretic response was greater in SHRs than in WKYs. There were
no significant differences in renal expression of betaine transporters between WKYs and
SHRs. Increased renal excretion of betaine contributes to decreased concentration of the
protective osmolyte in tissues of hypertensive rats. These findings pave the way for studies
evaluating a causal relation between depleted betaine and hypertensive organ damage,
including kidney injury
α/β Hydrolases: Toward Unraveling Entangled Classification
Get PDFα/β Hydrolase-like enzymes form a large and functionally diverse superfamily of proteins. Despite retaining a conserved structural core consisting of an eight-stranded, central β-sheet flanked with six α-helices, they display a modular architecture allowing them to perform a variety of functions, like esterases, lipases, peptidases, epoxidases, lyases, and others. At the same time, many α/β hydrolase-like families, even enzymatically distinct, share a high degree of sequence similarity. This imposes several problems for their annotation and classification, because available definitions of particular α/β hydrolase-like families overlap significantly, so the unambiguous functional assignment of these superfamily members remains a challenging task. For instance, two large and important peptidase families, namely S9 and S33, blend with lipases, epoxidases, esterases, and other enzymes unrelated to proteolysis, which hinders automatic annotations in high-throughput projects. With the use of thorough sequence and structure analyses, we newly annotate three protein families as α/β hydrolase-like and revise current classifications of the realm of α/β hydrolase-like superfamily. Based on manually curated structural superimpositions and multiple sequence and structure alignments, we comprehensively demonstrate structural conservation and diversity across the whole superfamily. Eventually, after detailed pairwise sequence similarity assessments, we develop a new clustering of the α/β hydrolases and provide a set of family profiles allowing for detailed, reliable, and automatic functional annotations of the superfamily members