Dim artificial light at night alters gene expression rhythms and growth in a key seagrass species (Posidonia oceanica).

Artificial light at night (ALAN) is a globally spreading anthropogenic stressor, affecting more than 20% of coastal habitats. The alteration of the natural light/darkness cycle is expected to impact the physiology of organisms by acting on the complex circuits termed as circadian rhythms. Our understanding of the impact of ALAN on marine organisms is lagging behind that of terrestrial ones, and effects on marine primary producers are almost unexplored. Here, we investigated the molecular and physiological response of the Mediterranean seagrass, Posidonia oceanica (L.) Delile, as model to evaluate the effect of ALAN on seagrass populations established in shallow waters, by taking advantage of a decreasing gradient of dim nocturnal light intensity (from < 0.01 to 4 lx) along the NW Mediterranean coastline. We first monitored the fluctuations of putative circadian-clock genes over a period of 24 h along the ALAN gradient. We then investigated whether key physiological processes, known to be synchronized with day length by the circadian rhythm, were also affected by ALAN. ALAN influenced the light signalling at dusk/night in P. oceanica, including that of shorter blue wavelengths, through the ELF3-LUX1-ZTL regulatory network, and suggested that the daily perturbation of internal clock orthologs in seagrass might have caused the recruitment of PoSEND33 and PoPSBS genes to mitigate the repercussions of a nocturnal stress on photosynthesis during the day. A long-lasting impairment of gene fluctuations in sites characterised by ALAN could explain the reduced growth of the seagrass leaves when these were transferred into controlled conditions and without lighting during the night. Our results highlight the potential contribution of ALAN to the global loss of seagrass meadows, posing questions about key interactions with a variety of other human-related stressors in urban areas, in order to develop more efficient strategies to globally preserve these coastal foundation species.

Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers.

OBJECTIVE: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline. METHODS: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT). RESULTS: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects. CONCLUSIONS: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.

Dandy-Walker malformation and variants: clinical features and associated anomalies in 28 affected children-a single retrospective study and a review of the literature.

OBJECTIVE: To investigate the clinical characteristics, the neuroimaging features and associated anomalies observed in children affected by Dandy-Walker malformations (DWM) and variants (DWV) in a single tertiary hospital in Catania and compare our data to their existent in the literature. METHODS: A retrospective case series using the medical records has been performed on 28 children diagnosed with DWM and DWV admitted to a single tertiary section of Pediatric Neurology, Department of Catania, Italy from January 2005 to January 2021. We reviewed the neuroimaging using the new diagnostic criteria of Klein et al. RESULTS: Associated anomalies were frequently reported. Among these, hydrocephalus was found in 13/28 (48%), and hydrocephalus plus corpus callosum anomalies in three children (10%). We described corpus callosum, cardiac and genitourinary anomalies in 2/28 (7%), 3/28 (10%), and 3/28 (10%), respectively. The most common clinical features were the developmental delay and epilepsy observed in 19/28 (67%) and in 9/28 (32%) of the cases. The first exam at the diagnosis was MRI in 17/28 patients, followed by transfontanellar ultrasound in 5/28, computed tomography in 4/28 and prenatal ultrasound in 2/28. To note, a child with DWM was affected by Down syndrome and one by congenital disorders of N-linked glycosylation (CDG-IId). CONCLUSIONS: Children with DWV were more commonly observed than children with DWM. Hydrocephalus is an anomaly, frequently and equally reported in both DWM and DMV. Perinatal complications were frequent adverse events with severe respiratory distress and need for cardiopulmonary resuscitation. Cognitive involvement and epilepsy were the most common comorbidities. Single DWV is associated with a better developmental outcome.

Correction: Evaluation of Whatman FTA cards for the preservation of yellow fever virus RNA for use in molecular diagnostics.

[This corrects the article DOI: 10.1371/journal.pntd.0010487.].

Microbiome structure in biofilms from a volcanic island in Maritime Antarctica investigated by genome-centric metagenomics and metatranscriptomics.

Antarctica is the coldest and driest continent on Earth, characterized by polyextreme environmental conditions, where species adapted form complex networks of interactions. Microbial communities growing in these harsh environments can form biofilms that help the associated species to survive and thrive. A rich body of knowledge describes environmental biofilm communities; however, most studies have focused on dominant community members rather than functional complexity and metabolic potential. To overcome these limitations, the present study used genome-centric metagenomics to describe two biofilm samples subjected to different temperature collected in Deception Island, Maritime Antarctica. The results unraveled a complex biofilm microbiome represented by 180 metagenome-assembled genomes. The potential metabolic interactions were investigated using metabolic flux balance analysis and revealed that purple bacteria are the community members with the highest correlations with other bacteria. Due to their predicted mixotrophic behavior, they may play a crucial role in the microbiome, likely supporting the heterotrophic species in biofilms. Metatranscriptomics results revealed that the chaperone system and proteins counteracting ROS and toxic compounds have a major role in maintaining bacterial cell homeostasis in sediments of volcanic origin.

Splenic abscesses in childhood brucellosis: a case-based review.

OBJECTIVE: Human brucellosis is a zoonosis with an extremely wide spectrum of clinical manifestations. Focal splenic involvement is very uncommon, particularly in the pediatric age group, during the illness' acute phase. CASE REPORT: A 4-year-old boy, already receiving third-generation cephalosporin treatment, was transferred from a local hospital to the University Pediatric Department for fever, anemia, increased inflammation index, and multiple, hyper-echogenic splenic lesions on abdominal ultrasound. Initial diagnostic laboratory investigations for Brucella infection, including the Widal-Wright test, were found to be negative. However, further diagnostic laboratory analysis using the chemiluminescent immunoassay was positive for Brucella IgM antibodies. Treatment with rifampicin at a dose of 150 mg/Kg/twice daily and co-trimethoprim at a dose of 80 mg/Kg/twice daily was started and continued for 7 weeks. IgM antibodies were undetectable after 2 weeks of treatment, and after 6 weeks of treatment, abdominal ultrasound documented a reduction of the diameter of the major splenic infiltrate from 1 to 0.5 cm. At 3 and 5 months of follow-up, re-evaluation of the abdominal lesions displayed complete resolution of the splenic lesions and a complete clinical recovery. CONCLUSIONS: The present case and a literature review are presented in this study since a standard diagnostic laboratory evaluation for brucellosis may miss the diagnosis, and in suspected cases, the laboratory analysis should be extended. Splenic abscesses are known to be rare in brucellosis, but the diagnosis should be considered in children with severe focal lesions, as specific antibiotic treatment may result in complete clinical recovery.

Evaluation of Whatman FTA cards for the preservation of yellow fever virus RNA for use in molecular diagnostics.

Yellow fever virus (YFV) is a flavivirus that frequently causes outbreaks of hemorrhagic fever in Africa and South America and is considered a reemerging public health threat. Accurate diagnosis of yellow fever (YF) disease is critical as one confirmed case constitutes an outbreak and may trigger a mass vaccination campaign. Highly sensitive and specific molecular diagnostics have been developed; however, these assays require maintenance of cold-chain during transport of specimens to prevent the degradation of viral RNA prior to testing. Such cold-chain requirements are difficult to meet in some regions. In this study, we investigated Whatman FTA cards as an alternative stabilization method of YFV RNA for use in molecular diagnosis. Using contrived specimens, linear regression analysis showed that RNA detection from a single 6mm FTA card punch was significantly less sensitive than traditional RNA extraction; however, pooling RNA extracted from two FTA punches significantly lowered the limit of detection to be equal to that of the traditional RNA extraction gold standard. In experiments addressing the ability of FTA card methodology to stabilize YFV RNA at variable temperature, RNA could be detected for more than two weeks following storage at 25°C. Even more promising, YFV RNA was detectable on cards held at 37°C from two days to over two weeks depending on viral input. FTA cards were also shown to stabilize YFV RNA at high humidity if cards were desiccated prior to inoculation. These results support that FTA cards could be cost effective and easy to use in molecular diagnosis of YF, preserving viral RNA to allow for positive diagnoses in situations where maintaining cold-chain is not feasible.

Defining comparative physiology: results from an online survey and systematic review.

August Krogh's 1929 principle is referenced as the cornerstone of comparative physiology (CP). However, there are diverse views as to what type of research falls under the CP approach. This study had three aims: 1) determine how CP is defined through an online survey (OS) of physiologists and a systematic review (SR), 2) put forth an updated definition of CP by summarizing OS and SR results, and 3) outline the numerous CP research approaches. Professional physiology societies (n = 54) were invited to share the OS with their members, and a SR was conducted, which yielded 197 and 70 definitions, respectively. The three most common words in descending order in the OS definitions were "different," "animals," and "species" and in the SR definitions, "animals," "species," and "organisms." The three most prevalent themes from the OS and SR definitions were comparing/differences/diversity across species (78% and 51%, respectively), response to the environment/ecology (28% and 43%, respectively), and included evolution or adaptation (24% and 60%, respectively). Ten research approaches were identified, which include broad comparison (i.e., many species generalization), specific comparison (e.g., 2 species; for traits that are different, exaggerated, extreme, missing, or not induced), or comparison while considering evolution (i.e., evolutionary physiology), ecology (i.e., ecophysiology), or human physiology/medicine. Only 5% and 33% of OS and SR definitions described or mentioned Krogh's principle. In conclusion, CP can best be defined as a compilation of research approaches that utilize different types of comparisons to elucidate physiological mechanisms and not simply comparing physiologies as the name implies.

The influence of the size and symmetry of cations and anions on the physicochemical behavior of organic ionic plastic crystal electrolytes mixed with sodium salts.

The phase behaviour, ionic conductivity, electrochemical stability and diffusion coefficients of mobile components in three organic ionic plastic crystals (OIPCs): triisobutylmethylphosphonium bis(fluorosulphonyl)amide (P1i444FSI), triisobutylmethylphosphonium bis(trifluromethanesulphonyl)amide (P1i444NTf2) and trimethylisobutylphosphonium bis(trifluoromethanesulphonyl)amide (P111i4NTf2) are compared to study the effect of the anions and cations on phase behaviour and dynamics. The FSI-based OIPC shows lower melting point and higher conductivity values most likely because of the higher degree of charge distributions and weaker ion-ion interactions compared to NTf2 anion-based OIPCs. Cyclic voltammetry of electrolytes consisting of these OIPCs with 70 mol% sodium salt incorporated indicates stable sodium plating/stripping behaviour at 70 and 50 °C for all samples. The magnitude of the peak currents, however, are much higher for the FSI-based electrolyte.

Stabilizing lithium metal using ionic liquids for long-lived batteries.

Suppressing dendrite formation at lithium metal anodes during cycling is critical for the implementation of future lithium metal-based battery technology. Here we report that it can be achieved via the facile process of immersing the electrodes in ionic liquid electrolytes for a period of time before battery assembly. This creates a durable and lithium ion-permeable solid-electrolyte interphase that allows safe charge-discharge cycling of commercially applicable Li|electrolyte|LiFePO4 batteries for 1,000 cycles with Coulombic efficiencies >99.5%. The tailored solid-electrolyte interphase is prepared using a variety of electrolytes based on the N-propyl-N-methylpyrrolidinium bis(fluorosulfonyl)imide room temperature ionic liquid containing lithium salts. The formation is both time- and lithium salt-dependant, showing dynamic morphology changes, which when optimized prevent dendrite formation and consumption of electrolyte during cycling. This work illustrates that a simple, effective and industrially applicable lithium metal pretreatment process results in a commercially viable cycle life for a lithium metal battery.

Effects of heavy metals on ultrastructure and Hsp70 induction in Lemna minor L. exposed to water along the Sarno River, Italy.

The effects of freshwater pollution in the highly contaminated river Sarno (Campania, Southern Italy) have been evaluated using bags containing the aquatic plant Lemna minor (Lemnacee, Arales), in order to determine morpho-physiological modifications as a response to pollutants. The exposition of Lemna bags for 7 days on three different sites along the river path showed alterations in chloroplasts and vacuoles shape and organization. Moreover, some specimens were exposed in vitro at the same heavy metal (HM) concentrations measured in the polluted sites of the river, and compared with data from the bag experiment; to verify the dose and time dependent effects, samples were exposed to HM in vitro at concentrations ranging from 10(-6) to 10(-4)M up to 7 days. Transmission electron microscopy (TEM) observations on in vitro plants confirmed that ultrastructural alterations affected most of plastids and the shape of different subcellular structures, namely vacuoles; in in vitro stressed specimens, Heat Shock Proteins 70 (Hsp70) levels changed, in dependence of changing levels of HM measured in different sites along the river path. Thus L. minor exhibited a possible correlation between the levels of HM pollution and Hsp70 occurrence; interestingly, the data presented showed that copper specifically increased Hsp70 levels at concentrations detected in polluted river waters, whereas cadmium and lead did not; on the other side, the latter represent highly toxic elements when specimens were exposed to higher levels in vitro. The effects of specific elements in vitro are compared to those observed in bags exposed along the river path; thus results are examined in order to propose L. minor as an organism able to be utilized to monitor heavy metals pollution; the possibility of using Hsp70s as specific markers of HM pollution is discussed.

Uptake and acute toxicity of cerium in the lichen Xanthoria parietina.

Environmental cerium (Ce) levels are likely to increase in the near future and monitoring of its biological effects will therefore be necessary. The aim of this study was to test if treatment of the lichen Xanthoria parietina with Ce-containing solutions (0.1mM, 1mM, 10mM and 100mM) causes Ce bioaccumulation (both extra- and intra-cellularly) as well as physiological (sample viability, membrane lipids peroxidation, photosynthetic performance, water-soluble proteins content) and ultrastructural alterations. The results showed that treatment with Ce solutions induces Ce bioaccumulation, both extra-cellularly and intra-cellularly, which in turn causes an acute toxicity, evident as decreased sample viability, marked decrease in the photosynthetic performance and important changes in the ultrastructure.

Bone marrow fibroblasts parallel multiple myeloma progression in patients and mice: in vitro and in vivo studies.

The role of cancer-associated fibroblasts (CAFs) has not been previously studied in multiple myeloma (MM). Here, cytofluorimetric analysis revealed higher proportions of bone marrow (BM) CAFs in patients with active MM (both at diagnosis and relapse) compared with patients in remission or those with monoclonal gammopathy of undetermined significance or deficiency anemia (controls). CAFs from MM patients produced increased levels of transforming growth factor-ß, interleukin-6, stromal cell-derived factor-1α, insulin-like growth factor-1, vascular endothelial growth factor and fibroblast growth factor-2 and displayed an activated and heterogeneous phenotype, which supported their origin from resident fibroblasts, endothelial cells and hematopoietic stem and progenitor cells via the endothelial-mesenchymal transition as well as mesenchymal stem cells via the mesenchymal transition, as both of these processes are induced by MM cells and CAFs. Active MM CAFs fostered chemotaxis, adhesion, proliferation and apoptosis resistance in MM cells through cytokine signals and cell-to-cell contact, which were inhibited by blocking CXCR4, several integrins and fibronectin. MM cells also induced the CAFs proliferation. In syngeneic 5T33MM and xenograft mouse models, MM cells induced the expansion of CAFs, which, in turn, promoted MM initiation and progression as well as angiogenesis. In BM biopsies from patients and mice, nests of CAFs were found in close contact with MM cells, suggesting a supportive niche. Therefore, the targeting of CAFs in MM patients may be envisaged as a novel therapeutic strategy.

Influence of vascular risk factors and neuropsychological profile on functional performances in CADASIL: results from the MIcrovascular LEukoencephalopathy Study (MILES).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown. METHODS: In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL). RESULTS: We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥ 2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (ß = -0.418, P < 0.003) in CADASIL patients and the executive function index (ß = -0.321, P = 0.028) in ARL. CONCLUSIONS: This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.

Antimony toxicity in the lichen Xanthoria parietina (L.) Th. Fr.

In this paper we tested if treating the lichen Xanthoria parietina with Sb-containing solutions causes Sb bioaccumulation as well as physiological and ultrastructural changes. Total and intracellular antimony content in Sb-treated samples increased progressively with increasing concentration in the treatment solutions. Incubation of X. parietina thalli with Sb at concentrations as low as 0.1mM caused a decrease in sample viability, measured as intensity of respiratory activity, and damage to cell membranes, expressed in terms of membrane lipid peroxidation, as well as ultrastructural changes such as plasmolysis, impairment of the thylakoid system of the alga and cytoplasmic lipid droplets. The photosynthetic system hardly responded, at least under the tested experimental conditions.

Notch-directed microenvironment reprogramming in myeloma: a single path to multiple outcomes.

Multiple myeloma is a deadly hematopoietic malignancy. Despite therapeutic advances such as autologous stem cell transplantation and novel chemotherapeutics, multiple myeloma remains incurable. Multiple myeloma cell localization in the bone marrow and the cross-talk with the bone niche trigger dramatic alterations in the bone marrow microenvironment critical for tumor progression, resistance to therapies and osteolytic bone destruction. It does not surprise that the molecular bases of such fatal interaction are under examination as source of novel potential pharmacological targets. Among these, the Notch family of receptors and ligands has gained growing interest in the recent years because of their early deregulation in multiple myeloma and their ability to affect multiple features of the disease, including tumor cell growth, drug resistance, angiogenesis and bone lesions. This review will explore the evidences of Notch deregulation in multiple myeloma, the state of the art of the currently known roles of its signaling in the fatal interaction between multiple myeloma cells, extracellular matrix and cells in the bone marrow stroma. Finally, we will present recent findings concerning the arguments for or against a therapy addressed to Notch signaling inhibition in the cure of multiple myeloma.

[Craniofacial morphology and obstructive sleep apnoea-hypopnoea syndrome: a craniometric comparative analysis]. / Morfologia craniofacciale e sindrome delle apnee-ipopnee ostruttive nel sonno: un'analisi craniometrica comparativa.

PURPOSE: The aim of this study was to define the relationship between paediatric obstructive sleep apnoea-hypopnea syndrome (OSAHS) and craniofacial morphovolumetric features through comparative craniometric analyses between affected children and controls based on conventional cephalometry. MATERIALS AND METHODS: Cephalometric examinations of 40 children affected by OSAHS were retrospectively evaluated. Sixteen craniometric landmarks were identified, and 27 linear and angular indices related to craniofacial morphovolumetric features were measured. Subsequently, the same process of identifying landmarks and measuring indices was performed on the cephalometric examinations of 40 controls. For each index, we then calculated in both groups the mean, standard deviation, standard error and p value. By comparing the values obtained in the two series, we calculated the degree of significance of each difference between children with OSAHS and controls using the Student t test. RESULTS: Differences of only 5/27 linear and angular indices considered were not statistically significant between groups, thus confirming susceptibility to the disorder in relation to certain splanchnocranic morphovolumetric features. The most significant differences involved mandibular plane inclination and distance between landmark sella and hyoid bone, a reliable index being the vertical position of the latter. CONCLUSIONS: Despite the limitations associated with the 2D nature of conventional cephalometry, mainly related to projection and identification errors, and despite the upright position during examination, we consider the diagnostic value and information content of this technique high, thus reaffirming its role as a first-line imaging investigation in children with sleep-related breathing disorders.

Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related macular degeneration patients.

BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655, a 19-nucleotide, O-methyl stabilized, double-stranded small interfering ribonucleic acid targeting the RTP801 gene in patients with neovascular age-related macular degeneration (AMD). METHODS: Prospective, phase 1, clinical multicentre trial, enrolled 27 patients with neovascular AMD unresponsive to prior treatment and best corrected visual acuity (BCVA) ≤ 20/200 in the study eye in stratum 1: (dose-escalating, open-label: 50 to 3000 µg of PF-04523655) and 27 patients who had potential to benefit from therapy and BCVA of ≤ 20/100 and ≥ 20/800 in stratum 2 (parallel, masked study of 1000, 1500, 2250, and 3000 µg of PF-04523655). The primary outcome was safety and tolerability assessment as well as pharmacokinetic profiling following a single IVT injection of PF-04523655. RESULTS: Doses of PF-04523655 ≥ 400 µg were generally detectable in the plasma at 1, 4, and 24 h post-injection. And all doses were below the lowest level of quantification by day 14. A single IVT injection of 50 to 3000 µg of PF-045237655 was generally safe and well tolerated over 24 months. There were no dose-limiting toxicities. CONCLUSION: A single IVT injection of PF-0523655 ≤ 3000 µg seems safe and well tolerated in eyes with neovascular AMD.

Toxicity, accumulation, and removal of heavy metals by three aquatic macrophytes.

A comprehensive understanding of the uptake, tolerance, and transport of heavy metals by plants will be essential for the development of phytoremediation technologies. In the present paper, we investigated accumulation, tissue and intracellular localization, and toxic effects of cadmium (Cd), lead (Pb), zinc (Zn), and copper (Cu) in three aquatic macrophytes (the angiosperms Lemna minor and Elodea canadensis, and the moss Leptodictyum riparium). We also tested and compared their capacity to absorb heavy metal from water under laboratory conditions. Our data showed that all the three species examined could be considered good bioaccumulators for the heavy metals tested. L. riparium was the most resistant species and the most effective in accumulating Cu, Zn, and Pb, whereas L. minor was the most effective in accumulating Cd. Cd was the most toxic metal, followed by Pb, Cu, and Zn. At the ultrastructural level, sublethal concentrations of the heavy metals tested caused induced cell plasmolysis and alterations of the chloroplast arrangement. Heavy metal removal experiments revealed that the three macrophytes showed excellent performance in removing the selected metals from the solutions in which they are maintained, thus suggesting that they could be considered good candidates for wastewaters remediation purpose.