Indigenous bacteria and bacterial metabolic products in the gastrointestinal tract of broiler chickens

The gastrointestinal tract is a dynamic ecosystem containing a complex microbial community. In this paper, the indigenous intestinal bacteria and the microbial fermentation profile particularly short chain fatty acids (SCFA), lactate, and ammonia concentrations are reviewed. The intestinal bacterial composition changes with age. The bacterial density of the small intestine increases with age and comprises of lactobacilli, streptococci, enterobacteria, fusobacteria and eubacteria. Strict anaerobes (anaerobic gram-positive cocci, Eubacterium spp., Clostridium spp., Lactobacillus spp., Fusobacterium spp. and Bacteroides) are predominating caecal bacteria in young broilers. Data from culture-based studies showed that bifidobacteria could not be isolated from young birds, but were recovered from four-week-old broilers. Caecal lactobacilli accounted for 1.5-24% of the caecal bacteria. Gene sequencing of caecal DNA extracts showed that the majority of bacteria belonged to Clostridiaceae. Intestinal bacterial community is influenced by the dietary ingredients, nutrient levels and physical structure of feed. SCFA and other metabolic products are affected by diet formulation and age. Additional studies are required to know the bacterial metabolic activities together with the community analysis of the intestinal bacteria. Feed composition and processing have great potential to influence the activities of intestinal bacteria towards a desired direction in order to support animal health, well-being and microbial safety of broiler meat.     

Sex differences in modulating blood brain barrier permeability by NO in pentylenetetrazol-induced epileptic seizures

Susceptibility to epilepsy as well as BBB dysfunction in some pathological conditions varies depending on sex difference. It has recently been shown that systemically given NO donor and antagonists modify the nature of seizures induced by PTZ (pentylenetetrazol) differently in male and female rats. This study investigates the role of NO on BBB permeability in PTZ seizures with sex differences using NO donor, sodium nitroprusside (SNP), and NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Nitrite+nitrate levels as indices of NO generation in the brain were also assessed. L-NAME prolonged seizure latency in male rats, seizure intensity and seizure duration were lessened. L-NAME depicted opposite effects in seizure nature in female rats. SNP prolonged seizure latency, while seizure intensity and duration were lessened only in female rats. L-NAME in male rats increased L-NAME use in female rats (not in male rats) which resulted in a more leaky BBB especially in midbrain, thalamus, hippocampus, corpus striatum and cerebellum whereas SNP use in male rats and not in female rats resulted in pronounced BBB opening in all brain regions studied than PTZ per se. L-NAME while decreasing nitrite+nitrate levels in male rat brains, acted in an opposite fashion in females. SNP use depicted an inverse picture with respect to L-NAME, with an opposite action in different sexes. This study reveals that NO effect on BBB in PTZ-induced seizures depends unequivocally on sex difference. The sex-dependent action of NO in seizures and in CNS pathologies warrants further investigation.     

Nanotechnology-Based Advancements in Postharvest Management of Horticultural Crops

Horticulture is a branch of Agricultural science where it is defined as the science and art of cultivating and handling fruits, vegetables, ornamental plants and several plants having unique medicinal and aromatic values. Horticultural crops provide farmers with high income and have good export quality, but they have a concern about postharvest losses. Hence, increasing productivity and decreasing post-harvest losses by using scientific studies and techniques like biotechnology and nanotechnology could be the simplest possible solution to the above-mentioned problems. Using nanotechnology which is having the characteristics of nanoparticles is proven to be very useful in science and technological applications. Nanotechnology-based formulations increase the product quality and the shelf life of horticultural products and provide multiple ways of inhibiting the growth and development of microorganisms. It is precisely a new edible packaging coverage (film) that controls the exchange of gases and prevents damage from harmful rays such as ultraviolet radiation to a greater extent. Increasing strength by using nano biosensors for labeling products is considered a fundamental process to automated control of storage products. Postharvest rotting of vegetables is recognized to be an oxidative reaction and microbial deterioration as well. This review will address all such nanotechnology-based advancements for minimizing post-harvest losses of horticultural crops and enhancing the socio-economical progress of growers in particular.     

Antagonistic Potential of Bacterial Species against Fungal Plant Pathogens (FPP) and Their Role in Plant Growth Promotion (PGP): A Review

Since the 19^th century to date, the fungal pathogens have been involved in causing devastating diseases in plants. All types of fungal pathogens have been observed in important agricultural crops that lead to significant pre and postharvest losses. The application of synthetic fungicide against the fungal plant pathogens (FPP) is a traditional management practice but at the same time these fungicides kill other beneficial microbes, insects, animal, and humans and are harmful to environment. The antagonistic microorganism such as bacteria are being used as an alternate strategy to control the FPP. These antagonistic species are cost-effective and eco-friendly in nature. These biocontrol bacteria have a broad mechanism against fungal pathogens present in the phyllosphere and rhizosphere of the plant. The antagonistic bacteria have different strategies against the FPP, by producing siderophore, biofilm, volatile organic compounds (VOCs), through parasitism, antibiosis, competition for limited resources and induce systemic resistance (ISR) in the host plant by activating the immune systems. The commercial bio-products synthesized by the major bacterial species Pseudomonas syringae, Burkholderia cepacia, Streptomyces griseoviridis, Pseudomonas fluorescens and Bacillus subtilis are used to control Fusarium, Pythium, Rhizoctonia, Penicillium, Alternaria, and Geotrichum. The commercial bio-formulations of bacteria act as both antifungal and plant growth regulators. The Plant growth-promoting rhizobacteria (PGPR) played a significant role in improving plant health by nitrogen-fixing, phosphorus solubilization, phytohormones production, minimizing soil metal contamination, and by ACC deaminase antifungal activities. Different articles are available on the specific antifungal activity of bacteria in plant diseases. Therefore, this review article has summarized the information on biocontrol activity of bacteria against the FPP and the role of PGPR in plant growth promotion. This review also provided a complete picture of scattered information regarding antifungal activities of bacteria and the role of PGPR.

     

Footprints of SARS-CoV-2 genome diversity in Pakistan, 2020–2021

The rapid spread of SARS-CoV-2 has significantly impacted the worldwide health system. The SARS-CoV-2 currently bears a remarkably low genetic diversity even though it carries one of the largest RNA genomes among viruses (Rausch et al., 2020). However, the coronaviruses harbor the capability of undergoing recombination at a high rate which can lead to the emergence of novel viral derivatives (Rausch et al., 2020; Gribble et al., 2021). This in turn requires not only global surveillance of SARS-CoV-2 genome in various countries but also careful scrutiny in animal genomic reservoirs. Conventionally, RNA viruses evolve with a high mutation rate, however, the presence of ExoN ribonuclease in SARS-CoV-2 genome has made its case different from other viral species (Gribble et al., 2021). The variables of natural selection which potentially drift the SARS-CoV-2 evolutionary dynamics can be recorded by analyzing deposited sequence genomes for its fitness, transmissibility potential, and pathogenicity (Rouchka et al., 2020). This can potentially provide a way to draw a holistic picture at a national level, while simultaneously providing a comparative overview with worldwide sequences.     

RNA Interference-Guided Targeting of Hepatitis C Virus Replication with Antisense Locked Nucleic Acid-Based Oligonucleotides Containing 8-oxo-dG Modifications

The inhibitory potency of an antisense oligonucleotide depends critically on its design and the accessibility of its target site. Here, we used an RNA interference-guided approach to select antisense oligonucleotide target sites in the coding region of the highly structured hepatitis C virus (HCV) RNA genome. We modified the conventional design of an antisense oligonucleotide containing locked nucleic acid (LNA) residues at its termini (LNA/DNA gapmer) by inserting 8-oxo-2’-deoxyguanosine (8-oxo-dG) residues into the central DNA region. Obtained compounds, designed with the aim to analyze the effects of 8-oxo-dG modifications on the antisense oligonucleotides, displayed a unique set of properties. Compared to conventional LNA/DNA gapmers, the melting temperatures of the duplexes formed by modified LNA/DNA gapmers and DNA or RNA targets were reduced by approximately 1.6-3.3°C per modification. Comparative transfection studies showed that small interfering RNA was the most potent HCV RNA replication inhibitor (effective concentration 50 (EC₅₀): 0.13 nM), whereas isosequential standard and modified LNA/DNA gapmers were approximately 50-fold less efficient (EC₅₀: 5.5 and 7.1 nM, respectively). However, the presence of 8-oxo-dG residues led to a more complete suppression of HCV replication in transfected cells. These modifications did not affect the efficiency of RNase H cleavage of antisense oligonucleotide:RNA duplexes but did alter specificity, triggering the appearance of multiple cleavage products. Moreover, the incorporation of 8-oxo-dG residues increased the stability of antisense oligonucleotides of different configurations in human serum.     

Molecular epidemiology of antibiotic-resistant genes and potent inhibitors against TEM,CTX-M-14, CTX-M-15, and SHV-1 proteins of Escherichia coli in district Peshawar,Pakistan

The Extended Spectrum Beta-Lactamases (ESBLs) producing bacteria is an issue of concern for clinicians resulting in minimize the treatment options. To overcome resistance mechanisms, novel inhibitors with good Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties must inhibit the ESBLs resistant genes. The current study aimed to identify the antibiotic resistance genes of ESBLs producing E. coli and a single inhibitor was designed to inhibit all the resistant proteins. The results showed that 42.9% ESBL producers had CTX-M (69.9%), TEM (63.4%), SHV (34.5%) and CTX-M-14 (17.5%) genes. The ESBLs producing isolates were resistant to cephalosporins, quinolones, and sulfonamide with Minimum Inhibitory Concentration (MICs) ranging from 64 to >256 μg/ml. To design multi inhibitory ligands, RECAP synthesis was used for the de-novo discovery of 1000 inhibitors database. Protein crystal structures were retrieved from Protein Data Base (PDB). Lipinski’s rules of five were applied to the novel inhibitors database to improve the ADMET properties. The novel inhibitors database was selected for docking simulations. Placement of the ligand was used by the London dG algorithm implemented in Molecular Operating Environment (MOE), while GBVI/WSA dG algorithm was used for final refinement. Based on docking score, visual inspection of ligands interaction with key residues, binding affinity, and binding energy of ligands with proteins, ten compounds were selected for ESBLs proteins with best ADMET properties, binding energy, and binding affinity the reported ones. These hits compounds have unique scaffolds and are predicted to be a starting point for developing potent inhibitors against antibiotic-resistant proteins.     

Nonselective β blockade attenuates the recruitment of CD62L? T lymphocytes following exercise

Exercise induces a selective redistribution of CD62L(-) T lymphocytes. This study examined the effects of beta adrenergic receptor blockade on this phenomenon. Twelve healthy men were exercised to exhaustion on a treadmill prior to and following 1 week of treatment with the nonselective beta antagonist propranolol or the beta1 selective antagonist metoprolol. Dynamic exercise resulted in a significant lymphocytosis (p < 0.001). CD8(+)CD62L(-) T cells showed a greater than 3-fold increase in response to exercise (p < 0.001) as compared to CD8(+)CD62L(+) T cells, which showed a more modest increase. Treatment with the nonselective beta antagonist propranolol significantly attenuated the preferential increase of circulating CD8(+)CD62L(-) lymphocytes (p = 0.01) but had no effect on CD8(+)CD62L(+) T cells. Treatment with the beta1 selective antagonist metoprolol did not affect the response of either subset. Our findings replicate a prior study indicating that CD62L expression influences T lymphocyte trafficking in response to exercise and extends those findings by showing that this phenomenon is mediated, in part, via the beta2-adrenergic receptor.     

Integrative analysis reveals methylenetetrahydrofolate dehydrogenase 1-like as an independent shared diagnostic and prognostic biomarker in five different human cancers

Background: Defects in methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression have earlier been examined in only a few human cancers. Objectives: Multi-omics profiling of MTHFD1L as a shared biomarker in distinct subtypes of human cancers. Methods: In the current study, for the multi-omics analysis of MTHFD1L in 24 major subtypes of human cancers, a comprehensive in silico approach was adopted to mine different open access online databases including UALCAN, Kaplan–Meier (KM) plotter, LOGpc, GEPIA, Human Protein Atlas (HPA), Gene Expression across Normal and Tumor tissue (GENT2), MEXPRESS, cBioportal, STRING, DAVID, TIMER, and Comparative Toxicogenomics Database (CTD). Results: We noticed that the expression of MTHFD1L was significantly higher in all the analyzed 24 subtypes of human cancers as compared with the normal controls. Moreover, MTHDF1L overexpression was also found to be significantly associated with the reduced overall survival (OS) duration of Bladder urothelial cancer (BLCA), Head and neck cancer (HNSC), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that MTHFD1L plays a significant role in the development and progression of these cancers. We further noticed that MTHFD1L was also overexpressed in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of MTHFD1L-associated genes in five diverse pathways. We also explored few interesting correlations between MTHFD1L expression and its promoter methylation, genetic alterations, CNVs, and between CD8+ T immune cells level. Conclusion: In conclusion, our results elucidated that MTHFD1L can serve as a shared diagnostic and prognostic biomarker in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features.     

Seasonal abundance estimates of cetaceans in the southern Black Sea (Sinop), Türkiye

The availability of reliable information on the abundance and distribution of threatened species is fundamental to evaluating their conservation status and taking the necessary measures to implement effective management. The seasonal abundance and distribution of cetaceans in the Sinop region, one of the essential fishing areas of the Black Sea, were estimated with line-transect data. Dedicated boat-based visual observations were conducted in four seasons between May 2019 and March 2020. Average estimates of abundance in the region over all seasons were 1,058 individuals for Black Sea harbor porpoises (Phocoena phocoena relicta; CV = 19.25%, 95% CI[725, 1,542]), 188 individuals for Black Sea bottlenose dolphins (Tursiops truncatus ponticus; CV = 21.67%, 95% CI[123, 289]), and 311 individuals for Black Sea common dolphin (Delphinus delphis ponticus; CV = 16.77%, 95% CI[123, 427]). The highest estimates for all three species were obtained in the spring. Harbor porpoises and bottlenose dolphins were present in the study area throughout the year, while common dolphins left the region in winter. These findings offer valuable insights that can guide and inform future conservation strategies, aligning with national and international frameworks for the protection of these cetacean species.