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Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.

The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf–Rayet stars 1 emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars 2 , 3 , leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion 4 . Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients 5 – 8 . Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf–Rayet stars may be the progenitors of some rapidly evolving transients. Observations of the supernova SN 2019hgp, identified about a day after its explosion, show that it occurred within a nebula of carbon, oxygen and neon, and was probably the explosion of a massive WC/WO star.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare 1 , 2 , followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating 3 . Early serendipitous observations 2 , 4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants. Using ultraviolet data as well as a comprehensive set of further multiwavelength observations of the supernova 2023ixf, a reliable bolometric light curve is derived that indicates the heating nature of the early emission.

Summary Lake Sturgeon is a potamodromous, fluvial‐dependent species from the family Acipenseridae, and one of the largest freshwater fishes within its North American range extending to the Great lakes, Mississippi River, and Hudson Bay drainages. Like almost all other sturgeon species, Lake Sturgeon populations throughout its range suffered mass declines or extirpation in the late 1800s into the early 1900s, due to extensive overexploitation and habitat loss and alteration. However, Lake Sturgeon are still present in low to high densities throughout their native range due primarily to factors including: the species long life span and resiliency, the remote location of many northern populations, long‐term pro‐active management programs effectively controlling exploitation, improved habitat and water‐quality conditions, and recovery programs that have been in effect since the late 1970s. Recovery programs initiated in the late 1970s are now just beginning to show signs of natural recruitment from populations re‐built with stocked fish. Large sustainable recreational Lake Sturgeon fisheries with annual harvests of up to 45 000 kg and a commercial fishery with an annual harvest of up to 80 000 kg still exist and are maintained for Lake Sturgeon due primarily to rigid regulations, harvest controls, enforcement, and user involvement. The prognosis for the species is generally good, although habitat loss and maintaining public interest in the species management and recovery continue to be the greatest threats to local and regional populations. Hydropower development, especially in the northern part of the species’ range, is especially challenging due to the potential negative impact this type of development can have on a long migrating fish like Lake Sturgeon. Advances in understanding Lake Sturgeon life history, habitat requirements, and distribution within and among water systems has strongly indicated that dams and Lake Sturgeon can co‐exist, if the correct planning and necessary mitigative techniques are employed at each site on a case‐by‐case basis.

An appropriate antibiotherapy is crucial for the safety and recovery of patients. Depending on the clinical conditions of patients, the required dose to effectively eradicate an infection may vary. An inadequate dosing not only reduces the efficacy of the antibiotic, but also promotes the emergence of antimicrobial resistances. Therefore, a personalized therapy is of great interest for improved patients’ outcome and will reduce in long-term the prevalence of multidrug-resistances. In this context, on-site monitoring of the antibiotic blood concentration is fundamental to facilitate an individual adjustment of the antibiotherapy. Herein, we present a bioinspired approach for the bedside monitoring of free accessible ß-lactam antibiotics, including penicillins (piperacillin) and cephalosporins (cefuroxime and cefazolin) in untreated plasma samples. The introduced system combines a disposable microfluidic chip with a naturally occurring penicillin-binding protein, resulting in a high-performance platform, capable of gauging very low antibiotic concentrations (less than 6 ng ml −1 ) from only 1 µl of serum. The system’s applicability to a personalized antibiotherapy was successfully demonstrated by monitoring the pharmacokinetics of patients, treated with ß-lactam antibiotics, undergoing surgery.

Summary Historical abundance and biomasss of lake sturgeon (Acipenser fulvescens Rafinesque, 1817) in the Great Lakes were estimated from historical commercial harvest data from 1879 to 1920 using two modeling techniques: a surplus production model with a Bayesian approach, and a depletion model. In addition, theoretical sustainable levels of exploitation and temporal recovery periods were estimated based on the surplus production model. The historical biomass of Lake Sturgeon in the Great Lakes during the period from 1879 to 1885 varied for each model and ranged from 313 900 to 6 473 000 kg (0.5–16.7 kg ha−1) using the surplus production model to 968 000 to 25 414 000 kg (2.4–31.7 kg ha−1) using the depletion model. The intrinsic population growth rate as determined from the surplus production model ranged from 0.079 to 0.123, and the theoretical sustainable exploitation rate ranged from 2.0 to 3.1%. The predicted recovery period for the overexploited populations was in excess of 60 years given recruitment assuming all other impediments to population recovery were removed.

Bendamustine has demonstrated clinical activity and a favorable safety profile as monotherapy or in combination with rituximab in lymphoid malignancies. As interventional trials do not always reflect clinical reality, we were interested in the treatment modalities and the outcome of bendamustine-based first-line therapy in patients with advanced indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL) in routine practice. Between April 2010 and October 2011, 324 patients were enrolled in a prospective non-interventional multicenter study. Choice of the bendamustine regimen was at the treating physician’s discretion. Effectiveness was assessed by best response. Mean age at onset of therapy was 69 years. The majority (94 %) of the patients was treated with bendamustine in combination with rituximab at a median bendamustine dose of 177 mg/m 2 per cycle. Most often, bendamustine was administered on days 1 and 2 (87 %) at 4-week intervals over a median of 6 cycles. Two hundred eighty-one patients qualified for evaluation of response. The overall response rate was 86 % (complete response 43 %, partial response 43 %, stable disease 10 %, progressive disease 4 %). Side effects of all grades were documented for 161 of the 323 patients (50 %), most frequently affecting blood/bone marrow (35 %). Fifty-four (17 %) patients experienced side effects of grade 3 (15 %) or grade 4 (2 %), and two patients grade 5 toxicities. Bendamustine-based first-line treatment of patients with advanced indolent NHL and MCL in clinical routine practice was assessed as effective and well tolerated in our study. Response was comparable to results from interventional clinical trials.

An extant stock of wild pallid sturgeon Scaphirhynchus albus persists in the fragmented upper Missouri River basin of Montana and North Dakota. Although successful spawning and hatch of embryos has been verified, long‐term catch records suggest that recruitment has not occurred for several decades as the extant stock lacks juvenile size classes and is comprised exclusively of large, presumably old individuals. Ages of 11 deceased (death years 1997–2007) wild S. albus (136–166 cm fork length) were estimated based on pectoral fin spines, sagittal otoliths and bomb radiocarbon (¹⁴C) assays of otoliths to test the hypothesis that members of this stock are old and to provide inferences on recruitment years that produced the extant stock. Age estimations based on counts of presumed annuli were about 2 years greater for otoliths (mean = 51 years, range = 43–57 years) than spines (mean = 49 years, range = 37–59 years). Based on ¹⁴C assays, confirmed birth years for all individuals occurred prior to 1957, thus establishing known longevity of at least 50 years. Estimated age based on presumed otolith annuli for one S. albus was validated to at least age 49. Although ¹⁴C assays confirmed pre‐1957 birth years for all S. albus, only 56% of estimated ages from spines and 91% of estimated ages from otoliths depicted pre‐1957 birth years. Both ageing structures were subject to under‐ageing error (up to 15 years). Lack of or severe curtailment of S. albus recruitment in the upper Missouri River basin since the mid‐1950s closely parallels the 1953–1957 timeframe when a mainstem reservoir was constructed and started to fill. This reservoir may function as a system‐wide stressor to diminish recruitment success of S. albus in the upper Missouri River basin.

It is well known that glutamatergic excitotoxicity and oxidative stress are implicated in the pathogenesis of hepatic encephalopathy (HE). The nucleoside guanosine exerts neuroprotective effects through the antagonism against glutamate neurotoxicity and antioxidant properties. In this study, we evaluated the neuroprotective effect of guanosine in an animal model of chronic HE. Rats underwent bile duct ligation (BDL) and 2 weeks later they were treated with i.p. injection of guanosine 7.5 mg/kg once a day for 1-week. We evaluated the effects of guanosine in HE studying several aspects: a) animal behavior using open field and Y-maze tasks; b) brain rhythm changes in electroencephalogram (EEG) recordings; c) purines and glutamate levels in the cerebral spinal fluid (CSF); and d) oxidative stress parameters in the brain. BDL rats presented increased levels of glutamate, purines and metabolites in the CSF, as well as increased oxidative damage. Guanosine was able not only to prevent these effects but also to attenuate the behavioral and EEG impairment induced by BDL. Our study shows the neuroprotective effects of systemic administration of guanosine in a rat model of HE and highlights the involvement of purinergic system in the physiopathology of this disease.