THE MOLLUSCAN ASSEMBLAGES IN THE FLUVIO-LACUSTRINE SUCCESSION OF THE PLIO-PLEISTOCENE MUGELLO BASIN (TUSCANY, ITALY)

New geologic studies on the fluvio-lacustrine Mugello Basin (Florence, Italy) stimulated a revision of the continental molluscan assemblages known since the last century. The fluvio-lacustrine succession has been subdivided in four synthems composed of fluvio-lacustrine (Torrente Ensa synthem, STE) and alluvial deposits (Scarperia, Luco di Mugello and Sagginale synthems). Two progressive angular unconformities in the STE allowed to distinguish three depositional sequences (S1, S2 and S3) composed of fan-delta gravels and sands, lacustrine silty clays (S1 and S2) and alluvial-fan gravels and sands (S3). Molluscs have been collected in various localities where S1 and S2 fan-delta and lacustrine deposits are exposed. The paleoecologic analysis of the molluscan assemblages is in accordance with the fluvio-lacustrine environment inferred from facies analysis. Different types of humid habitats, ranging from swamps, ponds, to channel-related environments (banks, leeves etc.), and open woody habitats have been recognized. The presence of Villafranchian extinct taxa such as Prososthenia oblonga, Emmericia cf. umbra and Tournouerina belnensis is in general agreement with the vertebrate fauna collected in the fluvio-lacustrine deposits since the last century and referred to the Tasso and Farneta faunal units (Late Villafranchian). A detailed integrated analysis of a 15 m thick gravelly-silty facies section of the S2 sequence reveals alternating depositional conditions in the subaerial portion of the fan deltas. Following a relative rise of base-level (i.e the lake level) flood-channels were disactivated with the formation of a floodplain-like environment dominated by fine-grained deposition, where localized poorly-drained areas created favourable habitats for molluscan taxa loving humid conditions. The sourrounding zones were characterized by open forests inhabited by terrestrial taxa. Low-magnitude, overland flows mixed the molluscan faunas of the different biotopes. The cyclic arrangement of gravels and silty clays reflects high-frequency uplift/denudational cycles during which biotopes for the molluscan fauna were alternatively activated.   SHORT NOTE

Recovery from Transient Global Amnesia Following Restoration of Hippocampal and Fronto–Cingulate Perfusion

A patient who suffered a transient global amnesia (TGA) attack underwent regional cerebral blood flow (rCBF) SPECT imaging and neuropsychological testing in the acute phase, after one month and after one year. Neuropsychological testing in the acute phase showed a pattern of anterograde and retrograde amnesia, whereas memory was within age normal limits at follow up. SPECT data were analysed with a within subject comparison and also compared with those of a group of healthy controls. Within subject comparison between the one month follow up and the acute phase detected increases in rCBF in the hippocampus bilaterally; further rCBF increases in the right hippocampus were detected after one year. Compared to controls, significant hypoperfusion was found in the right precentral, cingulate and medial frontal gyri in the acute phase; after one month significant hypoperfusion was detected in the right precentral and cingulate gyri and the left postcentral gyrus; after one year no significant hypoperfusion appeared. The restoration of memory was paralleled by rCBF increases in the hippocampus and fronto-limbic-parietal cortex; after one year neither significant rCBF differences nor cognitive deficits were detectable. In conclusion, these data indicate that TGA had no long lasting cognitive and neural alterations in this patient

Hydrocephalus onset after microsurgical or endovascular treatment for acute subarachnoid hemorrhage. Retrospective Italian Multicenter Study

Background: Chronic shunt-dependent hydrocephalus is a complication of aneurysmal subarachnoid hemorrhage (aSAH). Its incidence and risk factors have been described while the hydrocephalus onset in terms of days after treatment (microsurgical or endovascular) has not been yet analyzed. Materials and Methods: 45 patients, treated for aSAH in 4 Italian Neurosurgical Departments, were retrospectively analyzed. It was calculated the time that elapses between treatment and hydrocephalus onset in 36 patients. Results: Of the 45 shunted patients, 15 (33.3%) were included in the microsurgical group (group A) and 30 (66.6%) were in the endovascular one (group B). There was no difference of the hydrocephalus onset between the two groups (24,1 days, group A vs. 27,7 days, group B). The presence of intracerebral hematoma (ICH) caused a delay in the hydrocephalus onset after endovascular treatment in terms of 11,5 days compared to microsurgical group as well the absence of vasospasm determined a delay of 13,7 days (not statistically significant). Conclusion: No difference in terms of hydrocephalus onset after microsurgical or endovascular treatment has been demonstrated. Only the presence of ICH or the absence of vasospasm can cause a slight delay in the time of hydrocephalus onset in the endovascular series (not statistically significant). Long-term follow-up studies involving higher numbers of subjects are needed to better demonstrate this issue

Degenerative Jargon Aphasia: Unusual Progression of Logopenic/Phonological Progressive Aphasia?

Primary progressive aphasia (PPA) corresponds to the gradual degeneration of language which can occur as nonfluent/agrammatic PPA, semantic variant PPA or logopenic variant PPA. We describe the clinical evolution of a patient with PPA presenting jargon aphasia as a late feature. At the onset of the disease (ten years ago) the patient showed anomia and executive deficits, followed later on by phonemic paraphasias and neologisms, deficits in verbal short-term memory, naming, verbal and semantic fluency. At recent follow-up the patient developed an unintelligible jargon with both semantic and neologistic errors, as well as with severe deficit of comprehension which precluded any further neuropsychological assessment. Compared to healthy controls, FDG-PET showed a hypometabolism in the left angular and middle temporal gyri, precuneus, caudate, posterior cingulate, middle frontal gyrus, and bilaterally in the superior temporal and inferior frontal gyri. The clinical and neuroimaging profile seems to support the hypothesis that the patient developed a late feature of logopenic variant PPA characterized by jargonaphasia and associated with superior temporal and parietal dysfunction

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Threshold Switching by Bipolar Avalanche Multiplication in Ovonic Chalcogenide Glasses

Abstract An ovonic threshold switch (OTS) based on chalcogenide glasses finds application as a selecting device in storage class memory (SCM) arrays. The OTS operation relies on the threshold switching, where the device switches from the off to the on state without phase transition, then the device turns off almost immediately as the voltage is reduced below a certain holding value. The physics behind the switching phenomenon has attracted wide interest due to the complicated interplay between electronic transport, joule heating and phase transition. In this work, it is shown that the current‐voltage characteristic close to the switching point carries the fingerprint of carrier multiplication. The physical mechanism of threshold switching is then explained by bipolar impact ionization leading to avalanche multiplication, which in turn gives rise to the typical S‐shaped characteristic. Numerical simulations by this physics‐based model account for the measured switching properties, namely threshold voltage and current, at various chalcogenide thicknesses and compositions. These results provide the theoretical framework for future design and optimization of OTS in memory and computing applications