Avian ichnia and other vertebrate trace fossils from the Neogene Red Beds of Tarom valley in north-western Iran

The Neogene Red Beds of the Tarom valley (north-western Iran) include conglomerate, sandstone, marl and gypsum. Avian and mammal footprints were discovered in one of the sandstone layers at the base of a third Miocene stratigraphical unit in the Gilankesheh area located in the east Tarom valley. The avian ichnia include Aviadactyla vialovi, Avipeda filiportatis, Charadriipeda disjuncta, Charadriipeda isp. A and B and cf. Ornithotarnocia lambrechti. Bird feeding traces are preserved as bilobate, loop-shaped, sinusoidal and ring-like traces. We have also identified a reticulate texture of sole scale imprints in some of the avian ichnia. Two mammal footprints of camelid-like artiodactyls are also present with the avian ichno-assemblage.     

MMP‐3 (–1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)‐3 and correlate with severity of COPD: A study of MMP‐3, MMP‐7 and MMP‐12 in a Tunisian population

Background

The present study aimed to examine the role of matrix metalloproteinase (MMP)‐3 [(–1171) 5A/6A; Lys45Glu (A/G)], MMP‐7 [(–181) A/G] and MMP‐12 [(–82) A/G; Asn357Ser (A/G)] variants in the development and severity of chronic obstructive pulmonary disease (COPD) in Tunisians.

Methods

Plethysmography was performed in all participants to measure forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC parameters. Genotyping of MMP‐3, MMP‐7 and MMP‐12 polymorphisms was carried out in 138 patients with COPD and 216 healthy controls using a polymerase chain reaction–restriction fragment length polymorphism. Serum levels of MMPs and cytokines (interleukin‐6, tumor necrosis factor‐α) were determined by an enzyme‐linked immunosorbent assay.

Results

No significant correlations were observed between genetic variations in MMP‐3, MMP‐7 and MMP‐12 and the risk of development of COPD. Additionally, no impact of MMP‐7 (–181) A/G and MMP‐12 [(–82) A/G; Asn357Ser (A/G)] polymorphisms was observed on the respective protein levels and clinical parameters of the disease. Interestingly, both MMP‐3 (–1171) 5A/6A and Lys45Glu (A/G) variants were associated with respiratory function, as well as with serum levels of MMP‐3 in COPD patients. A relationship was found between the (–1171) 6A and 45Glu (G) alleles of the MMP‐3 gene and enhanced airflow limitation among COPD patients. Additionally, carriers of the 6A6A and 45 GG genotypes present higher MMP‐3 levels than noncarriers.

Conclusions

MMP‐3 (–1171) 5A/6A and Lys45Glu (A/G) polymorphisms were associated with the decline of lung function among COPD patients. These results could be linked to the upregulation of MMP‐3 in serum from COPD patients carrying the (–1171) 6A and 45 G homozygous genotypes.     

Disulfide bond formation protects Arabidopsis thaliana glutathione transferase tau 23 from oxidative damage

Background

Glutathione transferases play an important role as detoxifying enzymes. In A. thaliana, elevated levels of reactive oxygen species (ROS), provoked during biotic and abiotic stress, influence the activity of GSTU23. The aim of this study is to determine the impact of oxidative stress on the function and structure of GSTU23.

Sequence-specific recognition of DNA minor groove by an NIR-fluorescence switch-on probe and its potential applications

In molecular biology, understanding the functional and structural aspects of DNA requires sequence-specific DNA binding probes. Especially, sequence-specific fluorescence probes offer the advantage of real-time monitoring of the conformational and structural reorganization of DNA in living cells. Herein, we designed a new class of D2A (one-donor-two-acceptor) near-infrared (NIR) fluorescence switch-on probe named quinone cyanine–dithiazole (QCy–DT) based on the distinctive internal charge transfer (ICT) process for minor groove recognition of AT-rich DNA. Interestingly, QCy–DT exhibited strong NIR-fluorescence enhancement in the presence of AT-rich DNA compared to GC-rich and single-stranded DNAs. We show sequence-specific minor groove recognition of QCy–DT for DNA containing 5′-AATT-3′ sequence over other variable (A/T)4 sequences and local nucleobase variation study around the 5′-X(AATT)Y-3′ recognition sequence revealed that X = A and Y = T are the most preferable nucleobases. The live cell imaging studies confirmed mammalian cell permeability, low-toxicity and selective staining capacity of nuclear DNA without requiring RNase treatment. Further, Plasmodium falciparum with an AT-rich genome showed specific uptake with a reasonably low IC₅₀ value (<4 µM). The ease of synthesis, large Stokes shift, sequence-specific DNA minor groove recognition with switch-on NIR-fluorescence, photostability and parasite staining with low IC₅₀ make QCy–DT a potential and commercially viable DNA probe.     

Tristetraprolin inhibits Ras-dependent tumor vascularization by inducing vascular endothelial growth factor mRNA degradation

Vascular endothelial growth factor (VEGF) is one of the most important regulators of physiological and pathological angiogenesis. Constitutive activation of the extracellular signal-regulated kinase (ERK) pathway and overexpression of VEGF are common denominators of tumors from different origins. We have established a new link between these two fundamental observations converging on VEGF mRNA stability. In this complex phenomenon, tristetraprolin (TTP), an adenylate and uridylate-rich element-associated protein that binds to VEGF mRNA 3′-untranslated region, plays a key role by inducing VEGF mRNA degradation, thus maintaining basal VEGF mRNA amounts in normal cells. ERKs activation results in the accumulation of TTP mRNA. However, ERKs reduce the VEGF mRNA-destabilizing effect of TTP, leading to an increase in VEGF expression that favors the angiogenic switch. Moreover, TTP decreases RasVal12-dependent VEGF expression and development of vascularized tumors in nude mice. As a consequence, TTP might represent a novel antiangiogenic and antitumor agent acting through its destabilizing activity on VEGF mRNA. Determination of TTP and ERKs status would provide useful information for the evaluation of the angiogenic potential in human tumors.     

The public and private benefit of an impure public good determines the sensitivity of bacteria to population collapse in a snowdrift game

When cooperation is critical for survival, cheating can lead to population collapse. One mechanism of cooperation that permits the coexistence of cooperators and cheaters is an impure public good, whose public benefits are shared, but with a private benefit retained by the cooperator. It has yet to be determined how the contributions of the public and private benefit affect population survival. Using simulations and experiments with β-lactamase-expressing bacteria, we found that for a given amount of public and private benefit, the population was most sensitive to collapse when initiated from an intermediate fraction of cooperators due to the near-concurrent collapse of the cooperator and cheater populations. We found that increasing the ratio of public to private benefit increased sensitivity to collapse. A low ratio allowed cooperators to survive on their private benefit after the public benefit could not rescue the cheaters. A high ratio allowed the cheaters to survive to high concentrations of ampicillin due to the high public benefit. However, small increases in ampicillin caused a rapid decline in the entire population as the private benefit was insufficient to allow self-rescue of the cooperators. Our findings have implications in the persistence of populations that rely on cooperation for survival.     

A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy

Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.     

Effects of residue 5-point mutation and N-terminus hydrophobic residues on temporin-SHc physicochemical and biological properties

Temporin-SHc (FLSHIAGFLSNLF_amide) first isolated from skin extraction of the Tunisian frog Pelophylax saharica, which shows potent antimicrobial activity against Gram-positive bacteria and is highly active against yeasts and fungi without hemolytic activity at antimicrobial concentrations. The peptide adopts well-defined α-helical conformation when bound to SDS micelles. In this study, we explored the effects of residue at position 5 and the N-terminus hydrophobic character on the hydrophilic/polar face of temp-SHc, on its biological activities (antimicrobial and hemolytic) and biophysical properties (hydrophobicity, amphipathicity and helicity). Antibacterial and hemolytic properties of temporin-SHc derivatives depend strongly on physicochemical properties. Therefore, slight decreasing amphipathicity together with hydrophobicity and helicity by the substitution Ile⁵ → Leu decreased antimicrobial potency approximately twofold without changing of hemolytic activity. It is noteworthy that a conservative amino acid substitution decreases the antimicrobial activity, underlining the differences between Leu/Ile side chains insertion into the lipid bilayer. While the modification of N-terminal hydrophobic character by four residue inversion decreased amphipathicity (twofold) of (4-1)L₅temp-SHc and resulted in an increase in antibacterial activity against E. coli, E. faecalis and C. parapsilosis of at least fourfold, its therapeutic potential is limited by its drastic increase of hemolysis (LC₅₀ = 2 μM). We found that the percentage of helicity of temp-SHc analog is directly correlated to its hemolytic activity. Last, the hydrophobic N-terminal character is an important determinant of antimicrobial activity.     

Comparative toxicity of different chemical and biological insecticides against the scale insect Dactylopius opuntiae and their side effects on the predator Cryptolaemus montrouzieri

The contact toxicity of various chemical and biological pesticides for the first and second instar nymphs and adults of the Opuntia cochineal scale insect Dactylopius opuntiae and the predator ladybird Cryptolaemus montrouzieri was determined under Morocco semi field conditions. d-limonene (60?g/l) at 100 and 150?cc/hl, mineral oil (780?g/l) at 2400?cc/hl and malathion (500?g/l) at 300?cc/hl caused the highest mortality (99–100%) among first instar nymphs of D. opuntiae 24?h after treatment. d-limonene (60?g/l) at 150?cc/hl caused greatest mortality (99%) in second instar nymphs. The highest mortality (99%) among adult female D. opuntiae was observed 120?h after treatment with d-limonene (60?g/l) at 150?cc/hl and mineral oil (780?g/l) at 2400?cc/hl. For the predator C. montrouzieri the highest mortality (92–97%) among adults 24?h after treatment was caused by malathion (500?g/l) at 100, 200 and 300?cc/hl and alpha-cypermethrin (100?g/l) at 75, 150 and 225?cc/hl. The most harmful pesticides to C. montrouzieri larvae 24?h after treatment were malathion and alpha-cypermethrin with mortality rates of 89–95%. Mortality in larvae ranged from 87 to 100% 120?h after treatment with chlorpyriphos-methyl (480?g/l) at 75, 150 and 225?cc/hl and spinosad (480?g/l) at 100, 200 and 300?cc/hl. d-limonene (60?g/l) at 50?cc/hl and mineral oil (780?g/l) at 1000?cc/hl had the least impact on C. montrouzieri adults and larvae, causing mortality of 11 and 15%, respectively, 120?h after treatment. d-limonene (60?g/l) and mineral oil (780?g/l) may therefore be viable alternatives to others high-risk chemical pesticides. These two biological insecticides are effective in controlling the Opuntia cochineal scale insect but have little adverse impact on the predator C. montrouzieri.     

Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands: A prospective cohort study

BackgroundEmerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants.Methods and findingsIn a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231–556] and 214 [95% CI 153–299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11–30] and 14 [95% CI 8–25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02–0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data.ConclusionsOverall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination.

Marit J. van Gils and colleagues investigate antibody responses against diverse emerging SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands.