Extending the tephra and palaeoenvironmental record of the Central Mediterranean back to 430 ka: A new core from Fucino Basin, central Italy

Here we present the first tephrostratigraphic, palaeomagnetic, and multiproxy data from a new ∼98 m-deep sediment core retrieved from the Fucino Basin, central Italy, spanning the last ∼430 kyr. Palaeoenvironmental proxy data (Ca-XRF, gamma ray and magnetic susceptibility) show a cyclical variability related to interglacial-glacial cycles since the Marine Isotope Stage (MIS) 12-MIS 11 transition. More than 130 tephra layers are visible to the naked eye, 11 of which were analysed (glass-WDS) and successfully correlated to known eruptions and/or other equivalent tephra. In addition to tephra already recognised in the previously investigated cores spanning the last 190 kyr, we identified for the first time tephra from the eruptions of: Tufo Giallo di Sacrofano, Sabatini (288.0 ± 2.0 ka); Villa Senni, Colli Albani (367.5 ± 1.6 ka); Pozzolane Nere and its precursor, Colli Albani (405.0 ± 2.0 ka, and 407.1 ± 4.2 ka, respectively) and Castel Broco, Vulsini (419–490 ka). The latter occurs at the bottom of the core and has been 40Ar/39Ar dated at 424.3 ± 3.2 ka, thus providing a robust chronological constrain for both the eruption itself and the base of the investigated succession. Direct 40Ar/39Ar dating and tephra geochemical fingerprinting provide a preliminary radioisotopic-based chronological framework for the MIS 11-MIS 7 interval, which represent a foundation for the forthcoming multiproxy studies and for investigating the remaining ∼110 tephra layers that are recorded within this interval. Such future developments will contribute towards an improved MIS 11-MIS 7 Mediterranean tephrostratigraphy, which is still poorly explored and exploited

Pleistocene tephrostratigraphy and palaeoclimatology in the central Mediterranean region: ongoing research in Fucino Basin (central Apennines, Italy)

Palaeoclimatic records spanning beyond the radiocarbon range generally derive their chronologies from orbital tuning strategies. These chronologies can introduce a priori assumptions that are difficult to test and, possibly, circular arguments in palaeoclimatic reconstructions. We elaborate two high-resolution, multi-proxy and tephrochronologically-constrained records (F1-F3 and F4-F5) of past environmental and climatic changes in the central Mediterranean region. We perform geochemical (X-ray fluorescence scanning, carbon, nitrogen and sulphur elemental analysis through combustion), isotopic (C and O stable isotope mass spectrometry on bulk carbonates and organic matter), mineralogical (X-ray powder diffraction) and grain-size analyses on lacustrine marls recovered from palaeolake Fucino (Abruzzo, central Italy). Lacustrine sediments were acquired during two scientific drilling campaigns (F1-F3 and F4-F5) interesting the first ca. 85 m of the 1 km-thick and 2 Ma-old Fucino sedimentary succession. We make use of detailed tephrostratigraphic and tephrochronological frameworks to produce robust and independent chronologies based on new and published 40Ar/39Ar and 14C dating of tephra layers. On the basis of our chronologies, the F1-F3 and F4-F5 records continuously span over the last two glacial-interglacial cycles and over the last five glacial-interglacial cycles, respectively. We combine our geological data into proxies for catchment- and regional-scale environmental processes. Our proxy time-series depict prominent orbital and sub-orbital environmental changes that can be tracked in other lacustrine, marine and speleothem records across the Mediterranean and North Atlantic regions. Thanks to tephrostratigraphic correlations and chronological matching, we produce spatially coherent palaeoclimatic reconstructions recognising a complex interplay between regional environmental processes and broad-scale climatic events. We highlight strong orbital forcing for past climate changes

Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Malaltia de Parkinson; Fenotip; TremolorEnfermedad de Parkinson; Fenotipo; TemblorParkinson’s disease; Phenotype; TremorBackground and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.Solano Vila B. has received honoraria for educational presentations and advice service by UCB, Zambon, Teva, Abbvie, Bia

Diplopia is frequent and associated with motor and non-motor severity in parkinson's disease : Results from the COPPADIS cohort at 2-year follow-up

Background and objective: Diplopia is relatively common in Parkinson's disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as "with diplopia" or "without diplopia" according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269-4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012-1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson's Disease Rating Scale-III (OR = 1.039; 95%CI, 1.023-1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001-1.057; p = 0.049) scores were independent factors associated with diplopia (R = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease

Background: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. Methods: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. Results: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). Conclusions: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose

The Lake CHAd Deep DRILLing project (CHADRILL) - targeting ~ 10 million years of environmental and climate change in Africa

At present, Lake Chad ( ~13°0 N, ~14° E) is a shallow freshwater lake located in the Sahel/Sahara region of central northern Africa. The lake is primarily fed by the Chari-Logone river system draining a ~600 000 km2 watershed in tropical Africa. Discharge is strongly controlled by the annual passage of the intertropical convergence zone (ITCZ) and monsoon circulation leading to a peak in rainfall during boreal summer. During recent decades, a large number of studies have been carried out in the Lake Chad Basin (LCB). They have mostly focused on a patchwork of exposed lake sediments and outcrops once inhabited by early hominids. A dataset generated from a 673m long geotechnical borehole drilled in 1973, along with outcrop and seismic reflection studies, reveal several hundred metres of Miocene-Pleistocene lacustrine deposits. CHADRILL aims to recover a sedimentary core spanning the Miocene-Pleistocene sediment succession of Lake Chad through deep drilling. This record will provide significant insights into the modulation of orbitally forced changes in northern African hydroclimate under different climate boundary conditions such as high CO2 and absence of Northern Hemisphere ice sheets. These investigations will also help unravel both the age and the origin of the lake and its current desert surrounding. The LCB is very rich in early hominid fossils (Australopithecus bahrelghazali; Sahelanthropus tchadensis) of Late Miocene age. Thus, retrieving a sediment core from this basin will provide the most continuous climatic and environmental record with which to compare hominid migrations across northern Africa and has major implications for understanding human evolution. Furthermore, due to its dramatic and episodically changing water levels and associated depositional modes, Lake Chad's sediments resemble maybe an analogue for lake systems that were once present on Mars. Consequently, the study of the subsurface biosphere contained in these sediments has the potential to shed light on microbial biodiversity present in this type of depositional environment. We propose to drill a total of ~1800m of poorly to semi-consolidated lacustrine, fluvial, and eolian sediments down to bedrock at a single on-shore site close to the shoreline of present-day Lake Chad. We propose to locate our drilling operations on-shore close to the site where the geotechnical Bol borehole (13°280 N, 14°440 E) was drilled in 1973. This is for two main reasons: (1) nowhere else in the Chad Basin do we have such detailed information about the lithologies to be drilled; and (2) the Bol site is close to the depocentre of the Chad Basin and therefore likely to provide the stratigraphically most continuous sequence

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

The hidden biotic face of microbialite morphogenesis – a case study from Laguna de Los Cisnes, southernmost Patagonia (Chile)

Microbialites provide geological evidence into Earth's early ecosystems, recording long‐standing interactions between co‐evolving life and the environment. Yet, after more than 100 years of research, the complex interplay between environmental and biological forces involved in microbialite growth is still debated. Laguna de Los Cisnes, located in Chilean Tierra del Fuego, Patagonia, provides a unique opportunity to study these interactions. This lake, which became ice‐free around 10 000 years ago, features carbonate microbialites developed by algal–microbial communities. Macroscopically, the organo‐sedimentary deposits exhibit a consistent primary crater‐like architecture, showcasing macrostructural variations such as dish‐shaped, hemispherical, columnar and lenticular morphologies. This study explores the environmental and biological factors shaping microbialite macrostructure by analysing the distribution of dominant morphotypes across the basin. Concurrently, it examines the internal mesostructure and microstructure of microbialites in association with prevailing algal–microbial communities. The incremental development of these communities contributes to the distinct crater‐like morphology observed in microbialites from Laguna de Los Cisnes. The mineral encrustation of the green alga Percursaria percursa emerges as a primary driver of lithification, evidenced by the preservation of microfossils within the microstructure of the microbialites. Simultaneously, physical environmental factors, including waves, Langmuir cells and accommodation space influence the location of the algal–microbial carbonate factory, determining the spatial distribution and temporal succession of different crater architecture variants. Laguna de Los Cisnes, hosting well‐preserved subfossil outcrops and living microbialites, serves as a remarkable living laboratory for understanding microbialite morphogenesis. This study contributes to a novel model that captures the fundamental role of algal–microbial communities in determining the primary macrostructural architecture of microbialites before environmental factors come into play, merely reshaping this architecture into different morphotypes. </p

Combined Genomic and Imaging Techniques Show Intense Arsenic Enrichment Caused by Detoxification in a Microbial Mat of the Dead Sea Shore

Microbial mats and microbialites are essential tools for reconstructing early life and its environments. To better understand microbial trace element cycling, a microbial mat was collected from the sinkhole systems of the western shores of the Dead Sea, a dynamic environment exhibiting diverse extreme environments. Intense arsenic enrichment was measured (up to 6.5 million times higher than current concentrations in water, and 400 times the bulk concentration in the mat). Arsenic was found predominantly as As(V) in organic molecules, as shown by XANES spectra and high-resolution elemental mapping. Arsenic cycling genes obtained from metagenomic analysis were associated with arsenic detoxification, supporting an active mechanism of As(V) uptake, As(III) efflux and organoarsenic accumulation in the extracellular polymeric substances (EPS) of the mat. Thus, we propose that such localized As enrichment can be attributed to a transient increase in As(V) concentrations in the circulating subsurface water of the Dead Sea shore and its subsequent incorporation into organoarsenic molecules through microbial detoxification processes. Our data set supports the possibility of metalloid enrichment recorded in very localized facies due to rapid geogenic fluctuations in the chemistry of the water flowing over a biofilm. In this context, this example calls for caution in interpreting metal(loid) enrichment in organic matter-rich layers and microbialites of Paleoproterozoic origin. Arsenic signatures in Precambrian organic matter and carbonate rocks may host biosignatures, including evidence for extracellular polymeric substances, As-binding and detoxification processes, without supporting arsenotrophy. However, they provide clues to better assess the paleoenvironmental conditions at the time of microbial mat formation. Microbial mats and microbialites are like time machines helping us learn about ancient life and its environments. We collected a microbial mat from the unique Dead Sea's sinkholes, where life thrives in extreme conditions. In this mat, we found for the first time in this area a staggering 6.5 million-fold increase in arsenic, an element toxic to life. By closely studying the genes and chemistry of this microbial mat, we discovered that microbes were striving to clean up this excess arsenic in a sort of natural detoxification process. It seems that a temporary spike in arsenic levels in the Dead Sea water triggered this clean-up work, which eventually stored the arsenic safely in the mat away from the microbial cells. Our findings suggest that in the past, when microbial mats were one of the only ecosystems on Earth, changes in the water flowing over mats like this one could have caused similar accumulations of metals. Therefore, when scientists study ancient fossilized microbial layers, these discoveries can help us look into the past and understand the chemical and biological conditions under which these ancient microbial mats formed. Intense arsenic enrichment is detected for the first time around the Dead Sea Arsenic is accumulated in the organic matter of a microbial mat as methylated organoarsenic The enrichment results from microbial detoxification and may be fossilize