Search Results (42)

We present lightning-induced ionospheric perturbations in narrowband very-low-frequency (VLF) signals from the transmitters NWC (21.82° S, 114.17° E, 19.8 kHz) and VTX (8.4° N, 77.8° E, 18.6 kHz) recorded at the low-latitude station Dehradun (DDN; 30.3° N, 78.0° E) over a 12-month period from September 2020 to October 2021. Early/slow VLF events, VLF LOREs, and step-like VLF LOREs associated with lightning were analyzed for their onset and recovery times. This study utilized data from the World Wide Lightning Location Network (WWLLN), which provides lightning locations and energy estimates. The results show that early/slow VLF events occur most frequently, accounting for approximately 68% of cases, followed by VLF LOREs at 12%, and step-like VLF LOREs at 10%. Furthermore, we observed that 100% of the VLF perturbing events occurred during the nighttime, which is not entirely consistent with previous studies. Moreover, more than 60% of VLF LOREs were associated with lightning energies of approximately 1 kJ, and about 40% were associated with lightning energies of ~10 kJ. Step-like VLF LOREs were linked to WWLLN energies between 1 and 5 kJ. The observed WWLLN energy range is somewhat lower than the energies reported in previous studies. Scattering characteristics revealed that 87.3% of events were associated with wide-angle scattering, while approximately 12.6% were linked to narrow-angle scattering. LWPC version 2.1 was used to simulate these perturbing events and to estimate the reflection height (H′, in km) and the exponential sharpness factor (β, in km⁻¹) corresponding to changes in D-region electron density. The reflection height (H′, in km) and the exponential sharpness factor (β, in km⁻¹) of the D-region varied from 83 to 87 km and from 0.42 to 0.79 km⁻¹ for early/slow VLF events, from 83 to 85 km and from 0.5 to 0.75 km⁻¹ for step-like VLF LOREs, and from 81 to 83 km and from 0.75 to 0.81 km⁻¹ for VLF LOREs, respectively. Full article

We present coordinated observations from ozone Differential Absorption lidar (DIAL), aerosol lidar, and Doppler wind lidar at the City College of New York (CCNY) in northern Manhattan during the summer 2023 AGES+ campaigns across the New York City (NYC) region and Long Island Sound (LIS) areas. The results highlight significant ozone formation within the planetary boundary layer (PBL) and the concurrent transport of ozone/aerosol plumes aloft and mixing into the PBL during 26–28 July 2023. Especially, 26 July experienced the highest ozone concentration within the PBL during the three-day ozone episode despite having a lower temperature than the following two days. In addition, the onset of the afternoon sea breeze contributed to increased ozone levels in the PBL. A mobile ozone DIAL was also deployed at Columbia University’s Lamont–Doherty Earth Observatory (LDEO) in Palisades, NY, 29 km north of NYC, from 11 August to 8 September 2023. A notable high-ozone episode was observed by both ozone DIALs at the CCNY and the LDEO site during an unusual heatwave event in early September. On 7 September, the peak ozone concentration at the LDEO reached 120 ppb, exceeding the ozone levels observed in NYC. This enhancement was associated with urban plume transport, as indicated by wind lidar measurements, the HRRR (High-Resolution Rapid Refresh) model, and the Copernicus Sentinel-5 TROPOMI (TROPOspheric Monitoring Instrument) tropospheric column NO₂ product. The results also show that, during both heatwave events, those days with slow southeast to southwest winds experienced significantly higher ozone pollution. Full article

The gut microbiota consists of trillions of microorganisms, mostly bacteria, which establish a symbiotic relationship with the host. The host provides a favourable environment and the essential nutrients for their proliferation, while the gut microbiota plays a key role in maintaining the host’s health. Therefore, imbalances in its composition, a state known as dysbiosis, can contribute to the onset or progression of various pathological conditions, including atherosclerosis. Atherosclerosis is a chronic, slow-progressing inflammatory disease characterised by the formation and potential rupture of atheromatous plaques in medium- and large-calibre arteries. It underlies major cardiovascular events, such as stroke and myocardial infarction, and remains a leading cause of global morbidity and mortality. The modulation of the gut microbiota using prebiotics, probiotics, and faecal microbiota transplantation (FMT) has emerged as a promising approach for preventing and managing atherosclerosis. Although numerous studies have explored these strategies, further research is needed to establish their efficacy and mechanisms. This review explores the pathophysiology of atherosclerosis, its main risk factors, and the interplay between the gut microbiota and atherosclerosis, with a particular focus on the mechanisms by which microbiota-targeted interventions, including prebiotics, probiotics, and FMT, may serve as therapeutic adjuvants in the prevention and treatment of atherosclerosis. Full article

The warming climate and increasing extreme weather events are transforming ecological backgrounds, which is bringing new challenges to herders’ livelihood in grassland areas. To understand the practical ecological risks and the current resilience situations of herders’ behaviors and government correspondence measures, we built a conceptual framework of community resilience in pastoral areas, selected different kinds of steppes along the ecological gradient (desert steppe, typical steppe and meadow steppe) and took household surveys to recognize the difference in ecological risks and enhancing strategies in different grassland types. The results show that: (1) Herders in desert steppe, with the lowest precipitation and the worst grassland condition, turn out to have more experience in perceiving droughts and mitigating loss from disaster, but received the most attention from government assistance (28.0%) to getting through drought; (2) Typical steppe, with traditionally better pastural husbandry environment, suffered most broadly through droughts (85.7%) and have worst household livestock loss (26.7%) through snow storms; (3) Meadow steppe has the highest catastrophic snow storm ratio (65.0%) and affected ratio (95.0%), but the least assistance from the government (22.22%). The results revealed that originally high ecological vulnerability gradually encouraged herder’s livelihood adaptive capability. However, the government assistance and attention are more inclined to the local original ecological vulnerability. In addition, the increasing extreme climate events are bringing new challenges to adaptive knowledge systems of indigenous herders under good ecological condition. There is a clear need to combine the efforts of local pastoralists, policymakers and scientific community together to construct a more resilient socio-ecological pastoral systems under the global climate change. This research provides an in-depth understanding of community resilience in pastoral areas along the ecological gradient while facing the slow-onset climate change impacts. Practical recommendations on climate risk management and adaptation in pastoral areas are discussed. Full article

Background/Objectives: Charcot first described ALS in 1869, but the specific mechanisms that mediate the disease pathology are still not clear. Intense research efforts have provided insight into unique neuroanatomical regions, specific neuronal populations and genetic associations for ALS and other neurodegenerative diseases; however, the experimental results also suggest a convergence of these events to common toxic pathways. We propose that common toxic pathways can be therapeutically targeted, and this intervention will be effective in slowing progression and improving patient quality of life. Here, we focus on understanding the role of IL6 trans-signaling in ALS disease processes. Methods: We leveraged unique mouse models of IL6 trans-signaling that we developed that recapitulate the production of active sIL6R in a genotypic and quantitative fashion observed in humans. Given that the SOD1 transgenic mouse is one of the most highly studied and characterized models of ALS, we bred SOD1^G93A mice with IL6R trans-signaling mice to determine how enhanced trans-signaling influenced symptom onset and pathological processes, including neuromuscular junction (NMJ) denervation, glial activation and motoneuron (MN) survival. Results: The results indicate that in animals with enhanced trans-signaling, symptom onset and pathological processes were accelerated, suggesting a role in disease modification. Administration of an IL6R functional blocking antibody failed to alter accelerated symptom onset and disease progression. Conclusions: Future work to investigate the site-specific influence of enhanced IL6 trans-signaling and the tissue-specific bioavailability of potential therapeutics will be necessary to identify targets for precise therapeutic interventions that may limit disease progression in the 60% of ALS patients who inherit the common Il6R Asp³⁵⁸Ala variant. Full article

Although the Coronavirus disease 2019 (COVID-19) pandemic has ended, there are still many important lessons we can learn, as the pandemic profoundly affected every area of laboratory practice. During the pandemic, extensive changes to laboratory staffing had to be implemented, as many healthcare institutions required regular screening of all healthcare staff. Several studies examined the effectiveness of different screening regimens and concluded that repeated testing, even with lower sensitivity tests, could rival the performance of gold-standard RT-PCR testing in the detection of new cases. Many assay evaluations were performed both in the earlier and later periods of the pandemic. They included both nucleocapsid/spike antibodies and automated antigen assays. Early in the pandemic, it was generally agreed that the initial nucleocapsid antibody assays had poor sensitivity when used before 14 days of disease onset, with total or IgG antibodies being preferred over the use of IgM. Spike antibody assays gradually replaced nucleocapsid antibody assays, as most people were vaccinated. Spike antibodies tracked the rise in antibodies after vaccination with mRNA vaccines and became invaluable in the assessment of vaccine response. Studies demonstrated robust antibody secretion with each vaccine dose and could last for several months post-vaccination. When antigen testing was introduced, they became effective tools to identify affected patients when used serially or in an orthogonal fashion with RT-PCR testing. Despite the numerous findings during the pandemic period, research in COVID-19 has slowed. To this day it is difficult to identify a true neutralizing antibody test for the virus. An appropriate antibody level that would confer protective immunity against the plethora of new variants remains elusive. We hope that a summary of events during the pandemic could provide important insights to consider in planning for the next viral pandemic. Full article

Chordomas are a low-to-intermediate-grade slow-growing subtype of sarcoma, but show propensity to grow and invade locally with recurrence and metastasis in 10–40% of cases. We describe the first case of spontaneous regression of a solid tumor (histologically and immunohistochemically proven chordoma) after COVID-19. A female patient with clival chordoma underwent occipitocervical fixation prior to tumor resection. In the early post-operative stage following the arthrodesis procedure, she was diagnosed with COVID-19. Six months after COVID-19, she finally came back for endoscopic endonasal resection of the tumor and pre-operative MRI surprisingly showed 98.9% regression of the tumor volume. Tumor resection was performed, and both histopathological and immunohistochemistry confirmed diagnosis of chordoma with positive brachyury levels. She showed improvement of right hemiparesis and left-sided tongue palsy. The tumor was comprised of tumor-infiltrating inflammatory cells. CD3 and CD68 were positive, suggesting the presence of T-lymphocytes and macrophages. CD20 and CD56 were negative, suggesting the absence of B-lymphocytes and NK-cells. The authors believe that the onset of COVID-19 exacerbated the patient’s immune response and improved anti-tumor immunity. It was concluded that T-cells, which are involved in the COVID-19 immune response and were found infiltrating the tumor, acted as a critical pathway to this event. Further studies are encouraged in order to gain a better understanding of the SARS-CoV-2–chordoma interaction. Full article

Disturbance or insufficiency of the tear film challenges the regulatory systems of the ocular surfaces. The reaction of the surfaces includes temporary mechanisms engaged in the preservation of homeostasis. However, strong or persisting challenges can lead to the potential exhaustion of the coping capacity. This again activates the vicious circle with chronic inflammation and autocatalytic deterioration. Hence, the factors challenging the homeostasis should be addressed in time. Amongst them are a varying osmolarity, constant presence of small lesions at the epithelium, acidification, attrition with mechanical irritation, and onset of pain and discomfort. Each of them and, especially when occurring simultaneously, impose stress on the coping mechanisms and lead to a stress response. Many stressors can culminate, leading to an exhaustion of the coping capacity, outrunning normal resilience. Reaching the limits of stress tolerance leads to the manifestation of a lubrication deficiency as the disease we refer to as dry eye disease (DED). To postpone its manifestation, the avoidance or amelioration of stress factors is one key option. In DED, this is the target of lubrication therapy, substituting the missing tear film or its components. The latter options include the management of secondary sequelae such as the inflammation and activation of reparative cascades. Preventive measures include the enhancement in resilience, recovery velocity, and recovery potential. The capacity to handle the external load factors is the key issue. The aim is to guard homeostasis and to prevent intercellular stress responses from being launched, triggering and invigorating the vicious circle. Considering the dilemma of the surface to have to cope with increased time of exposure to stress, with simultaneously decreasing time for cellular recovery, it illustrates the importance of the vicious circle as a hub for ocular surface stress. The resulting imbalance triggers a continuous deterioration of the ocular surface condition. After an initial phase of the reaction and adaption of the ocular surface to the surrounding challenges, the normal coping capacity will be exhausted. This is the time when the integrated stress response (ISR), a protector for cellular survival, will inevitably be activated, and cellular changes such as altered translation and ribosome pausing are initiated. Once activated, this will slow down any recovery, in a phase where apoptosis is imminent. Premature senescence of cells may also occur. The process of prematurization due to permanent stress exposures contributes to the risk for constant deterioration. The illustrated flow of events in the development of DED outlines that the ability to cope, and to recover, has limited resources in the cells at the ocular surface. The reduction in and amelioration of stress hence should be one of the key targets of therapy and begin early. Here, lubrication optimization as well as causal treatment such as the correction of anatomical anomalies (leading to anatomical dry eye) should be a prime intent of any therapy. The features of cellular stress as a key hub for the vicious circle will be outlined and discussed. Full article

Background: Epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early onset, and unfavorable developmental outcomes. This article discusses the use of intravenous methylprednisolone (IVMP) pulse therapy in pediatric patients with EE to evaluate its efficacy and tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction > 50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: The study included 21 patients, with a responder rate of 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Variables significantly predicting favorable outcome were etiology (p = 0.0475) and epilepsy type (p = 0.0475), with the best outcome achieved in patients with genetic epilepsy and those with encephalopathy related to electrical status epilepticus during slow-wave sleep (ESES). All patients evidenced improvements in QoL at the last follow-up, with no relevant adverse events reported. Conclusions: Our study confirmed the efficacy and high tolerability of IVMP pulse therapy in pediatric patients with EE. Genetic epilepsy and ESES were positive predictors of a favorable clinical outcome. QOL, EEG tracing, and postural–motor development showed an improving trend as well. IVMP pulse therapy should be considered earlier in patients with EE. Full article

Generating rapid, easy-to-interpret community data for drinking reservoirs as a means of tackling water quality management is of increasing demand within the water industry. Taste and odour (T&O) is one of many increasing concerns to water companies worldwide, incurring huge costs as customer complaints accumulate and additional treatment and resource management are required. However, there remains a two-fold issue in addressing T&O management: firstly, predicting the initial onset of a T&O event relies on a highly complex understanding of environmental considerations and their interaction with T&O-related taxa, and secondly, there remains a lag between the notification of a T&O event and the resolution of the issue by reservoir management staff. This is partly due to slow, low-resolution methods of detecting and reliably identifying problem taxa in samples. These methods are unable to provide information on the huge plethora of taxa related to T&O metabolite production and often cannot provide data in a timely enough manner for an opportune management response. This means the water industry is often forced to use a reactive, rather than proactive, approach to water quality monitoring. Here, we present methods for implementing a high-throughput sequencing approach to monitoring drinking reservoirs for water quality and improving the sustainability of water supplies, as well as methods for presenting these data on easy-to-interpret data dashboards that can be updated rapidly as new data are generated. Our methods and dashboarding approaches are currently being trialled and tested within the UK water industry, and so here, we show anonymised examples of those data presentations. We propose that these methods can greatly aid reservoir management teams in their approach to T&O monitoring and can be used to implore more sustainable management pipelines, safeguarding future water sources. Full article

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag⁺ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery. Full article

Accurate measurements and predictions of near-surface soil drying and evaporation following heavy rainfall events are often needed for research in agriculture and hydrology. However, such measurements and predictions at mine waste pile and tailing settings are limited. The prediction of evaporation at mine waste piles is essential for many problems in geotechnical engineering, including the design of soil cover systems for the long-term closure of hazardous waste sites, and thus mitigates, for example, the generation of acid mine drainage (AMD) and metal leaching. AMD is one of mining’s most serious threats to the environment. This study investigated the short-term (8 days) and medium-term (27 days) drying rates and evaporative fluxes at the surface and near-surface of the Deilmann South waste-rock (DSWR) pile at the Key Lake uranium mine, northern Saskatchewan, using the gravimetric (GV) method and SoilCover (SC) model, respectively, during and following heavy rainfall events for the environment. The SC simulation results showed that during the weather-controlled stage (Stage I) of the first 5-day period of rainfall events, while the surface was wet, the potential evaporation (PE) was equal to the actual evaporation (AE) (i.e., AE/PE = 1). As the surface became drier on Day 6, the cumulative PE began to separate from the cumulative AE and the surface’s drying rate rapidly diverged from those at the deeper depths. This occurrence signaled the onset of the soil profile property-controlled stage (Stage II). As the drying continued, the surface became desiccated and the slow-rate drying stage (Stage III) was established from Day 7 onward. The SC-simulated AE results were compared to those measured using the eddy covariance (EC) method for the same test period at the DSWR pile in a different study. The comparison showed that the two methods yielded similar AE results, with 18% relative errors. The results of this study provided the opportunity to validate the SC model using actual data gathered under field conditions and to ascertain its ability to accurately predict the PE and AE at the surfaces of mine waste piles. Full article

Recent critical events brought attention to the increasing exposure of urban environments to both slow and rapid onset disasters, which arise from both anthropogenic and natural causes. These events have particularly severe effects on historic centres, which are characterized by high levels of vulnerability and valuable assets exposed to risk. To minimize the impact on tangible and intangible cultural heritage values, especially in outdoor public areas such as squares and streets, it is crucial to establish coherent mitigative and adaptive solutions for different types of hazards. This research presents a methodology aimed at defining levels of multi-vulnerabilities in historic districts in the Apulia Region (Italy), considering the recurrent hazards to which the latter is prone. It uses a multi-step process based on structured and non-structured methodologies and tools for single risks, examined in combination, to determine the main properties characterizing the vulnerability assessment. The dataset was analyzed in a GIS environment to evaluate the selected Apulian case study (Molfetta) in Multi-Asynchronous Hazard scenarios, showing the compounded levels of criticalities for open areas and streets. This information is intended to support authority and emergency managers in identifying priority interventions and increasing the resilience of the outdoor public places. Full article

Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive redox environment may be a central function of sleep. Therefore, biochemical manipulations that potentiate cellular antioxidant pathways may facilitate this function of sleep. N-acetylcysteine increases cellular antioxidant capacity by serving as a precursor to glutathione. In mice, we observed that intraperitoneal administration of N-acetylcysteine at a time of day when sleep drive is naturally high accelerated the onset of sleep and reduced NREMS delta power. Additionally, N-acetylcysteine administration suppressed slow and beta electroencephalographic (EEG) activities during quiet wake, further demonstrating the fatigue-inducing properties of antioxidants and the impact of redox balance on cortical circuit properties related to sleep drive. These results implicate redox reactions in the homeostatic dynamics of cortical network events across sleep/wake cycles, illustrating the value of timing antioxidant administration relative to sleep/wake cycles. A systematic review of the relevant literature, summarized herein, indicates that this “chronotherapeutic hypothesis” is unaddressed within the clinical literature on antioxidant therapy for brain disorders such as schizophrenia. We, therefore, advocate for studies that systematically address the relationship between the time of day at which an antioxidant therapy is administered relative to sleep/wake cycles and the therapeutic benefit of that antioxidant treatment in brain disorders. Full article

Despite their uniqueness, the ontogeny and differentiation of the single-lobed gonads in the poeciliids are very poorly understood. To address this, we employed both cellular and molecular approaches to systematically map the development of the testes and ovary in Gambusia holbrooki from pre-parturition to adulthood, encompassing well over 19 developmental stages. The results show that putative gonads form prior to the completion of somitogenesis in this species, a comparatively early occurrence among teleosts. Remarkably, the species recapitulates the typical bi-lobed origin of the gonads during early development that later undergoes steric metamorphosis to form a single-lobed organ. Thereafter, the germ cells undergo mitotic proliferation in a sex-dependent manner before the acquisition of the sexual phenotype. The differentiation of the ovary preceded that of the testes, which occurred before parturition, where the genetic females developed meiotic primary oocytes stage I, indicating ovarian differentiation. However, genetic males showed gonial stem cells in nests with slow mitotic proliferation at the same developmental stage. Indeed, the first signs of male differentiation were obvious only post-parturition. The expression pattern of the gonadosoma markers foxl2, cyp19a1a, amh and dmrt1 in pre- and post-natal developmental stages were consistent with morphological changes in early gonad; they were activated during embryogenesis, followed by the onset of gonad formation, and a sex-dimorphic expression pattern concurrent with sex differentiation of the ovary (foxl2, cyp19a1a) and testes (amh and dmrt1). In conclusion, this study documents for the first time the underlying events of gonad formation in G. holbrooki and shows that this occurs relatively earlier than those previously described for ovi- and viviparous fish species, which may contribute to its reproductive and invasive prowess. Full article