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Abstract Parthenogenesis, or virgin birth, describes a mode of reproduction where an egg develops into an offspring without fertilization, and is observed across various vertebrate taxa, excluding mammals. Obligate parthenogenesis, found in around 100 vertebrate species and 1000 invertebrate species, is relatively rare. Conversely, facultative parthenogenesis, where females can reproduce both sexually and parthenogenetically, is observed in some vertebrates, including elasmobranchs. Notably, this phenomenon in elasmobranchs is mainly documented in captivity, allowing for detailed long-term observation. Specifically, this study reports the first case of facultative parthenogenesis in the common smooth-hound shark Mustelus mustelus, a species classified by IUCN as endangered. Here we show that the juvenile M. mustelus were born through parthenogenesis, exhibiting homozygosity at each genetic marker, consistent with terminal fusion automixis. Remarkably, this finding reveals that parthenogenesis can occur annually in these sharks, alternating between two females, and conclusively excludes long-term sperm storage as a cause. Consequently, this enhances our understanding of parthenogenesis in elasmobranchs and highlights the reproductive flexibility of M. mustelus. Overall, these results contribute to our broader understanding of reproductive strategies in elasmobranchs, which could inform conservation efforts for endangered species.

This study investigates the biomass production and growth strategies of the relict seagrass Zostera marina, a species sensitive to high temperatures, within the Venice Lagoon (Italy). Monthly data collected from January to December 2019 and November 2020 to October 2021 in a single station in proximity of one lagoon port-entrance, along with seasonal data from 2018 and 2021 for the whole lagoon, were analyzed in conjunction with environmental parameters and macroalgal presence. The objective was to understand the impact of climate changes, particularly rising water temperatures, on the cover, standing crop and net primary production of Z. marina and the effect of the MoSE gate closures designed to protect Venice from high-water events. Despite expectations of a decline due to temperature increase and reduced water exchange, our findings reveal a notable adaptability of Z. marina, with increases in both cover and biomass. This resilience suggests that Z. marina can counteract environmental challenges, making this study relevant for broader ecological and conservation contexts beyond the Venice Lagoon.

Seagrasses play a vital role in marine ecosystems worldwide. However, until recently these ecosystems were experiencing declines due to various global and local threats. In response to this issue, initiatives have been launched to combat seagrass loss by addressing local and regional major stressors and actively engaging in restoration efforts by transplantation. Although seagrass restoration has progressed significantly with the development of numerous transplant techniques, these are not always crowned with success. This is often due to the fact that the environmental parameters of water, sediment and biota of the recipient sites are not carefully considered in their suitability for transplantation. In this study, the multi-year experiences and data from numerous environmental surveys in transitional water systems have been condensed to define limit values for the ideal growth conditions and the extreme values in which the survival of four aquatic angiosperm species is possible: Cymodocea nodosa, Zostera marina, Zostera noltei and Ruppia cirrhosa. Approaches to transplants, seasonality and critical issues have been explored. The identified limits and parameters of water, sediment and biota will help to define the suitability of a recipient site for the rooting of seagrasses, increasing the chances of success for transplant operations.

Abstract 55 million people worldwide suffer from Alzheimer's disease (AD). A definitive diagnosis of AD is made postmortem after a neuropathological examination of the brain. There is an urgent need for an innovative, noninvasive methodology that allows for an early and reliable diagnosis. Several engineered phages that recognized Aβ‐autoantibodies present in the sera of AD patients are previously identified. Here, novel phages are tested for their ability to accurately discriminate AD sera using immunophage‐polymerase chain reaction in a miniatured biochip. It is found that five of the six phages analyzed discriminate between healthy controls and AD patients. Further, by combining the response of two phages, non‐AD and severe AD cases are identified with 100% accuracy and mild‐to‐moderate cases with 90% accuracy. While the number of cases used here are relatively small and can be confirmed in larger cohorts, this first‐of‐a‐kind system represents an innovative methodology with the potential of having a major impact in the AD field: from a clinical perspective, it can aid physicians in making an accurate AD diagnosis; from a research perspective, it can be used as a surrogate for AD clinical trials.

Molecular subtypes of small cell lung cancer characterized by neuroendocrine differentiation have been described in cell lines and primary tumors. The clinical implications of neuroendocrine subtypes in metastatic and relapsed tumors, and the extent to which the subtype distribution is recapitulated in patient-derived models remains unclear. Here, the authors integrated genomics and transcriptomics on 100 small cell cancers from a range of metastatic sites finding complex intra- and intertumoral heterogeneity, notably not recapitulated in patient-derived model systems, and distinct therapeutic vulnerabilities associated with neuroendocrine subtypes.

Abstract The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human–environment interactions during Humankind history.

In the last decade, the Venice Lagoon showed a significant environmental recovery that changed the assemblages of macroalgal and aquatic angiosperm dominant species and significantly increased the primary production. The decreasing of anthropogenic impacts, such as eutrophication and clam harvesting, favored a strong reduction of Ulvaceae, replaced by species with higher ecological value, and the recolonization of aquatic angiosperms. Consequently, hypo-anoxic conditions, once frequently occurring in the lagoon, have been considerably reduced and aquatic angiosperms have recolonized the area, covering 94.8 km2 in comparison to the 55.9 km2 recorded in 2003 (+70%). Cymodocea nodosa, Zostera marina, and Zostera noltei expanded by 37.5%, 44.6%, and 191%, respectively, with a significant increase in biomass and primary production. In late spring 2018, angiosperms showed a standing crop of approximately 372 ktonnes (+77%) and a net primary production of approximately 1189 ktonnes FW (+67%). In the meantime, Ruppia cirrhosa, which since the 1980s had disappeared from the lagoon areas subjected to tidal expansion, but was still present in some fishing valleys, recolonized the bottoms of the northern lagoon with meadows of over 6 km2; this accounted for a standing crop and net primary production of 8.9 and 18.0 ktonnes, respectively. Based on surveys carried out in 2021, ecological conditions are still improving, and this is increasing both the biodiversity and the production of macroalgae and aquatic angiosperms.

OBJECTIVES:To investigate the correlation between histogram-based Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI) parameters and positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG-PET) values in oropharyngeal squamous cell carcinoma (OPSCC), both in primary tumors (PTs) and in metastatic lymph nodes (LNs). METHODS:52 patients with a new pathologically-confirmed OPSCC were included in the present retrospective cohort study. Imaging including DCE-MRI and 18F-FDG PET/CT scans were acquired in all patients. Both PTs and the largest LN, if present, were volumetrically contoured. Quantitative parameters, including the transfer constants, Ktrans and Kep, and the volume of extravascular extracellular space, ve, were calculated from DCE-MRI. The percentiles (P), P10, P25, P50, P75, P90, and skewness, kurtosis and entropy were obtained from the histogram-based analysis of each perfusion parameter. Standardized uptake values (SUV), SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated applying a SUV threshold of 40%. The correlations between all variables were investigated with the Spearman-rank correlation test. To exclude false positive results under multiple testing, the Benjamini-Hockberg procedure was applied. RESULTS:No significant correlations were found between any parameters in PTs, while significant associations emerged between Ktrans and 18F-FDG PET parameters in LNs. CONCLUSIONS:Evident relationships emerged between DCE-MRI and 18F-FDG PET parameters in OPSCC LNs, while no association was found in PTs. The complex relationships between perfusion and metabolic biomarkers should be interpreted separately for primary tumors and lymph-nodes. A multiparametric approach to analyze PTs and LNs before treatment is advisable in head and neck squamous cell carcinoma (HNSCC).

While an ischemic insult poses a lethal danger to myocardial cells, a significant proportion of cardiac myocytes remain viable throughout the ischemic episode and die, paradoxically, only after the blood flow is reinstated. Despite decades of research, the actual chronology of critical events leading to cardiomyocyte death during the reperfusion phase remains poorly understood. Arguably, identification of the pivotal event in this setting is necessary to design effective strategies aimed at salvaging the myocardium after an ischemic attack. Here we used neonatal rat ventricular myocytes (NRVMs) subjected to 20-30 min of simulated ischemia followed by 1 hour of "reperfusion". Using different combinations of spectrally-compatible fluorescent indicators, we analyzed the relative timing of the following events: (1) abnormal increase in cytoplasmic [Ca2+] (TCaCy); (2) abnormal increase in mitochondrial [Ca2+] (TCaMi); (3) loss of mitochondrial inner membrane potential (ΔΨm) indicating mitochondrial permeability transitions (TMPT); (4) sacrolemmal permeabilization (SP) to the normally impermeable small fluorophore TO-PRO3 (TSP). In additional experiments we also analyzed the timing of abnormal uptake of Zn2+ into the cytoplasm (TZnCy) relative to TCaCy and TSP. We focused on those NRVMs which survived anoxia, as evidenced by at least 50% recovery of ΔΨm and the absence of detectable SP. In these cells, we found a consistent sequence of critical events in the order, from first to last, of TCaCy, TCaMi, TMPT, TSP. After detecting TCaCy and TCaMi, abrupt switches between 1.1 mM and nominally zero [Ca2+] in the perfusate quickly propagated to the cytoplasmic and mitochondrial [Ca2+]. Depletion of the sarcoplasmic reticulum with ryanodine (5 μM)/thapsigargin (1 μM) accelerated all events without changing their order. In the presence of ZnCl2 (10-30 μM) in the perfusate we found a consistent timing sequence TCaCy < TZn ≤ TSP. In some cells ZnCl2 interfered with Ca2+ uptake, causing "steps" or "gaps" in the [Ca2+]Cy curve, a phenomenon never observed in the absence of ZnCl2. Together, these findings suggest an evolving permeabilization of NRVM's sarcolemma during reoxygenation, in which the expansion of the pore size determines the timing of critical events, including TMPT.

Spontaneous phenotypic heterogeneity confers a population-level advantage to cells that are exposed to fluctuating environments. Here the authors show that the endothelium of some organs displays a dynamic mosaicism in expression of Von Willebrand factor, suggesting bet hedging as a strategy for adaptive homeostasis.

A prominent theory of cell death in myocardial ischemia/reperfusion (I/R) posits that the primary and pivotal step of irreversible cell injury is the opening of the mitochondrial permeability transition (MPT) pore. However, the predominantly positive evidence of protection against infarct afforded by the MPT inhibitor, Cyclosporine A (CsA), in experimental studies is in stark contrast with the overall lack of benefit found in clinical trials of CsA. One reason for the discrepancy might be the fact that relatively short experimental ischemic episodes (

The Gram-negative bacterium Pseudomonas aeruginosa is one of the most dreaded pathogens in the hospital setting, and represents a prototype of multi-drug resistant "superbug" for which effective therapeutic options are very limited. The identification and characterization of new cellular functions that are essential for P. aeruginosa viability and/or virulence could drive the development of anti-Pseudomonas compounds with novel mechanisms of action. In this study we investigated whether TolB, the periplasmic component of the Tol-Pal trans-envelope protein complex of Gram-negative bacteria, represents a potential drug target in P. aeruginosa. By combining conditional mutagenesis with the analysis of specific pathogenicity-related phenotypes, we demonstrated that TolB is essential for P. aeruginosa growth, both in laboratory and clinical strains, and that TolB-depleted P. aeruginosa cells are strongly defective in cell-envelope integrity, resistance to human serum and several antibiotics, as well as in the ability to cause infection and persist in an insect model of P. aeruginosa infection. The essentiality of TolB for P. aeruginosa growth, resistance and pathogenicity highlights the potential of TolB as a novel molecular target for anti-P. aeruginosa drug discovery.

BackgroundThe ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-detected brown adipose tissue (BAT), is enhanced by cold stimulus and modulated by other factors that still have to be disentangled. We investigated the prevalence, mass, and glucose-uptake activity of ¹⁸F-FDG-detected BAT in a population of adults living in the temperate climatic zone of the Rome area.Methods and findingsWe retrospectively analyzed 6454 patients who underwent ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) examinations. We found ¹⁸F-FDG BAT in 217 of the 6454 patients (3.36%). Some of them underwent more than one scan and the positive scans were 278 among 8004 (3.47%). The prevalence of patients with at least one positive scan was lower in men (1.77%; 56 of 3161) compared with women (4.88%; 161 of 3293). The BAT positive patients were most frequently younger, thinner and with lower plasma glucose levels compared with BAT negative patients. The amount of BAT in the defined region of interest, the activity of BAT and the number of positive sites of active BAT were similar in both sexes. The prevalence of patients with ¹⁸F-FDG positive PET/CT was highest in December-February, lower in March-May and September-November, and lowest in June-August and was positively correlated with night length and negatively correlated with ambient temperature. Changes in day length and variations of temperature, associated with the prevalence of positive BAT patients. Among the patients who had multiple scans, outdoor temperature was significantly lower and day length was shorter on the occasion when BAT was detected.ConclusionsThis study identifies day length, outdoor temperature, age, sex, BMI, and plasma glucose levels as major determinants of the prevalence, mass, and activity of ¹⁸F-FDG-detected BAT.