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Rising daily temperatures and water shortage are two of the major concerns in agriculture. In this work, we analysed the tolerance traits in a tomato line carrying a small region of the Solanum pennellii wild genome (IL12-4-SL) when grown under prolonged conditions of single and combined high temperature and water stress. When exposed to stress, IL12-4-SL showed higher heat tolerance than the cultivated line M82 at morphological, physiological, and biochemical levels. Moreover, under stress IL12-4-SL produced more flowers than M82, also characterized by higher pollen viability. In both lines, water stress negatively affected photosynthesis more than heat alone, whereas the combined stress did not further exacerbate the negative impacts of drought on this trait. Despite an observed decrease in carbon fixation, the quantum yield of PSII linear electron transport in IL12-4-SL was not affected by stress, thereby indicating that photochemical processes other than CO2 fixation acted to maintain the electron chain in oxidized state and prevent photodamage. The ability of IL12-4-SL to tolerate abiotic stress was also related to the intrinsic ability of this line to accumulate ascorbic acid. The data collected in this study clearly indicate improved tolerance to single and combined abiotic stress for IL12-4-SL, making this line a promising one for cultivation in a climate scenario characterized by frequent and long-lasting heatwaves and low rainfall.

Background COVID-19 is an infectious illness, featured by an increased risk of thromboembolism. However, no standard antithrombotic therapy is currently recommended for COVID-19 hospitalized patients. Aim of this study was to evaluate safety and efficacy of additional therapy with aspirin over prophylactic anticoagulation (PAC) in COVID-19 hospitalized patients and its impact on survival. Methods 8168 patients hospitalized with COVID-19 were enrolled in a multicenter-international prospective registry (HOPE COVID-19). Clinical data and in-hospital complications, including mortality, were recorded. 344 patients with incomplete data were excluded. Study population included patients treated with PAC or with PAC and aspirin. A comparison of clinical outcomes between patients treated with PAC and PAC and aspirin was performed using an adjusted analysis with propensity score matching. Results Of 7824 patients, 360 (4.6%) received PAC and aspirin and 2949 (37.6%) PAC. Propensity-score matching yielded 298 patients from each group. Mean age was 73±11 years, 67% were male, prevalence of hypertension and diabetes was 79 and 33% respectively and 7.5% underwent invasive ventilation. In the propensity score-matched population, cumulative incidence of in-hospital mortality was lower in patients treated with PAC and aspirin vs PAC (15% vs 21%, Log Rank p=0.01, Figure 1). At multivariable analysis in propensity matched population of COVID-19 patients, including age, sex, hypertension, diabetes, kidney failure and invasive ventilation, aspirin treatment was associated with lower risk of in-hospital mortality (HR 0.62, CI 95% 0.42–0.92, p=0.018). Conclusions Additional therapy with aspirin over PAC in COVID-19 hospitalized patients was associated with lower mortality risk in a propensity score matched population. Funding Acknowledgement Type of funding sources: None.

In her book Specifications Grading, Linda B. Nilson advocates for a grading regimen she claims will save faculty time, increase student motivation, and improve the quality and rigor of student work. If she is right, there is a strong case for many faculty to adopt some version of the system she recommends. In this paper, we argue that she is mostly right and recommend that faculty move away from traditional grading. We begin by rehearsing the central features of specifications grading and providing two examples of how to implement it in philosophy classes. In light of the examples, we argue that specifications grading fulfills two of Nilson’s central desiderata (increasing rigor and motivating students) but not the third (saving faculty time). Since specifications grading generates two benefits that when combined increase student learning, without adding or increasing burdens, we conclude that student learning increases when courses are revised to include aspects of specifications grading.

Organic semiconductors, including graphitic carbon nitride (g-C3N4, CN), represent an important class of materials for the development of novel antimicrobial or biomedical technologies. Of principal interest is the ability of these materials to catalyze the reduction of elemental oxygen to generate reactive oxygen species (ROS), including hydrogen peroxide (H2O2). Here, we describe the fabrication of photoactive van der Waals heterojunctions incorporating 1,4,5,8-naphthalene tetracarboxylic dianhydride (NTCDA) and CN. The composite heterojunction systems were characterized by a combination of physical (TEM, SEM, pXRD), spectroscopic (FT-IR, XPS, DRUV, photoluminescence, TCSPC) and kinetic experiments. Electronic interactions between the two components of the heterojunction increase the rate of photochemical production of H2O2 from elemental oxygen by 410%, relative to samples of pure CN. Mechanistic analysis reveals that interaction of NTCDA with the surface of CN modifies the mechanism of H2O2 formation in the heterojunction photocatalysts. The photochemical production of H2O2 by irradiation of the most active heterojunction composition is sufficient to reduce the viability of E. coli O157:H7, S. aureus and Ps. aeruginosa PAO1 by 99%. Importantly, H2O2 production by the NTCDA/CN heterojunctions suppresses Ps. aeruginosa biofilm formation, even at light exposure doses that had a lesser impact on overall planktonic cell growth.

Electrocatalytic reduction of waste nitrate to ammonium provides a circular process with reduced carbon dioxide emissions compared to current nitrate treatment and ammonia production processes. However, electrocatalysts require a delicate balance between a surfaces’ activity for the competing hydrogen evolution (HER) and nitrate reduction reactions (NO3RR). We measure ammonium Faradaic efficiencies (FEs) of several transition metals (TMs) ranging from 3.6±6.6% (on Ag) to 93.7±0.9% (on Co) in neutral buffered media. A microkinetic model identifies competitive adsorption between nitrate and hydrogen adatoms (H*) as the origin of voltage-dependent nitrate rate order. NO3RR FE is described via competition for electrons with the HER, decreasing sharply for TMs with high work function or hydrogen adsorption energy. Density functional theory calculations indicate Co maximizes ammonium selectivity by: (1) binding intermediate nitrite strongly to enable subsequent reduction; and (2) promoting subsequent nitric oxide dissociation, leading to selective reduction of nitrogen adatoms (N*) to ammonium.

Since the 2018 IAEA FEC Conference, FTU operations have been devoted to several experiments covering a large range of topics, from the investigation of the behaviour of a liquid tin limiter to the runaway electrons mitigation and control and to the stabilization of tearing modes by electron cyclotron heating and by pellet injection. Other experiments have involved the spectroscopy of heavy metal ions, the electron density peaking in helium doped plasmas, the electron cyclotron assisted start-up and the electron temperature measurements in high temperature plasmas. The effectiveness of the laser induced breakdown spectroscopy system has been demonstrated and the new capabilities of the runaway electron imaging spectrometry system for in-flight runaways studies have been explored. Finally, a high resolution saddle coil array for MHD analysis and UV and SXR diamond detectors have been successfully tested on different plasma scenarios.

Background Several studies have shown that Takotsubo syndrome (TTS) secondary to neurological disorders is associated with higher rate of in-hospital complications. Imaging brain studies found that atrophy or damage of some regions and their altered connectivity with other brain regions are typical features of TTS patients. Aim of the study To evaluate rates of in hospital and long-term follow up events in TTS patients with history or acute cerebrovascular events (CVE). Methods 395 consecutive patients were enrolled in a multicenter prospective registry. History, clinical data, echocardiographic parameters and in-hospital and long-term follow up events of all patients were evaluated. Results Prevalence of CVE among TTS patients was 9.4% (N=37). Compared to the control group, these patients were older (80±7 vs 71±12 years, p=0.01) and predominantly men (24% vs 9%, p=0.01). No differences in terms of cardiovascular risk factors and left ventricular ejection fraction at admission and discharge were found between the two groups. The prevalence of physical stressors was higher in the CVE group (67% vs 44% p=0.01). The incidence of in-hospital adverse events was higher in the CVE group (70% vs 29%), mainly driven by higher rates of cardiogenic shock (19 vs 8%, p=0.01) and in-hospital death (19 vs 4%, p=0.01). At long-term follow-up, patients in the CVE group had higher mortality rates (38% vs 20%, p=0.01). Patients presenting with acute CVE, 10 out of 37 patients (27%), when compared with chronic CVE had higher in-hospital mortality rates (40% vs 11%, p=0.01). Conclusion TTS patients with history or CVE had higher rates of in-hospital events and death at long-term follow-up. Acute CVEs in the setting of TTS are associated with a worse prognosis. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Ospedali Riuniti di Foggia. Università di Foggia

Much of leftist political philosophy has uncritically accepted the logic of capitalism, which is a logic of conservation that presents itself as a logic of “production.” Many leftist political philosophers subscribe to capitalism’s fundamental myth—that capitalism produces the new. This appearance of proliferation, however, masks an underlying stasis. This article interrogates this trend in the apparently disparate projects of contemporary accelerationism and Jacques Rancière. The accelerationist project of immanence allows for newness only in quantity and not in quality, while Rancière, coming closer to thinking radical newness in his account of politics, forecloses the possibility of a radically emancipatory society. I suggest an open ontology, which Marx offers, provides a better framework for thinking revolutionary newness.

This article argues that Jan-Werner Müller in “What Spaces Does Democracy Need?” overemphasizes the danger for democratic engagement inherent in the medium of the internet. It claims that the main problem with online discourse is one that comes from without and one that faces in-person discourse as well, and that is the danger of increased privatization and the erosion of a truly public sphere. Nonetheless, online sites can and do still play an important role in our political projects, a role that is not necessarily less significant than the role that physical sites play.

Precollege philosophy programs provide young people with alternative spaces to ask questions and develop critical perspectives on their experiences, but neoliberal school management practices make the creation of these spaces increasingly difficult. Relying on my own experience as an instructor of a community-engaged course that focuses on precollege philosophy, I investigate how college and university professors and students can create philosophical learning opportunities for high school students without participating in the culture of volunteerism demanded by neoliberal logic. I argue that the work my university students perform in the community-engaged course is a win-win that undermines neoliberalism’s assault on education by providing high school students with a valuable opportunity while helping my students achieve important skills.

Evidence for performance deficits in psychopathic offenders on emotional processing tasks have been documented. However, studies that show performance improvements or elimination of anomalies under certain conditions are not consistent with a general insensitivity to emotion stimuli. The current study tests the hypothesis set forth by the Affect Regulation Theory (Penney and Kosson, manuscript submitted to Clinical Psychological Science) that psychopathic participants’ performance on an affective lexical decision task will reflect a speed-accuracy trade-off wherein accuracy on emotion-word trials correlates with response latency among psychopathic participants but not controls. Participants were 86 incarcerated male offenders divided into three groups using scores on the Psychopathy Checklist-Revised and DSM-IV criteria for ASPD (non-ASPD/non-psychopathic, ASPD/non-psychopathic; and ASPD + psychopathic). There was a significant Group x Response latency interaction for negative word trials, with greater accuracy associated with slower response times on negative word trials for ASPD + psychopathic individuals but not for the other groups. The implications of these results for hypotheses about emotional functioning in psychopathic offenders and for the recently proposed ART are discussed.

Introduction. Nursing management aimed to prevent viral infection in order to promote care plans that reduce the SARS-CoV-2 infection as much as possible. Evidence acquisition. There were different studies focusing on small case series on Covid-19 pregnant women and on logistic management in order to reduce the risk of contagion. Evidence synthesis. A review of the primary and the secondary literature was carried out in the Clinical Key and the PubMed databases. The bibliographic research was focused on the critical reading of the studies from 1 February 2020 to 30 June 2020. A total of eight articles analyzed special measures necessary to prevent Covid-19 in the pregnant women by implementing algorithms to be shared in a multidisciplinary context, also on challenges in the nursing care and in proposals for future studies. Conclusions. Since there were few data available on the Covid-19 positive pregnant women, further developments of studies and more appropriate protocols were needed on this particular topic. © 2021, EDRA S.p.A. All rights reserved.

Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity.

A new “on water” MW-assisted esterification protocol using fatty chlorides and acetonidehydroxytyrosol as starting materials, giving rise to a one-pot multistep reaction, without any added catalyst is described. The reaction took place at the interface oil/water thus being strictly dependent on the lipophilicity of the fatty acid acyl chloride. The potential scale-up of the method was also reported.

The psychopathic individual is characterized by limited affective experiences, is known to act impulsively and often antisocially, but also seems calm and at ease in the presence of others (Cleckley, The mask of sanity, Mosby, St. Louis, MO, 1941/1996; Hare, Manual for the Hare Psychopathy Checklist—Revised, Multi-Health Systems, Toronto, ON, 2003). Psychopathic individuals are present in significant numbers within the criminal justice system, where their persistent antisocial behavior strains both human and financial resources. Upon release they are more likely to reoffend than nonpsychopathic offenders, resulting in greater cost to their communities and—typically—return to the system (Hemphill et al., Legal Criminol Psychol 3: 139–170, 1998). Despite the seriousness of this syndrome, little systematic research has been conducted examining treatment within this population. Based on early negative conceptualizations, strengthened by a small number of documented treatment failures, psychopathic individuals have been described as “untreatable”. More recently, some evidence suggests that, although they are less likely to retain in treatment than non-psychopathic individuals, adult offenders with psychopathy who complete intensive CBT and risk-reduction oriented treatment programs respond similarly to these interventions as nonpsychopathic offenders. In this chapter, research in this area is reviewed, with an emphasis on placing early research in context and identifying the gaps in the existing literature. Specifically, the chapter includes: (1) review of the assessment and prevalence of psychopathy across diverse groups; (2) review and discussion of early research on the treatment of psychopathy; and (3) review and discussion of more recent intervention research, including studies with adults and adolescents. Overall, although it appears that there may be some treatments that impact positively the functioning of psychopathic individuals, it is not clear yet the extent or duration of these benefits. Moving forward, information regarding the responses of psychopathic individuals to existing treatments must be collected, and interventions targeted to this resistant group must be developed and systematically tested. Despite some advances, the field as a whole is still in the early stages of development and growth is urgently needed.

Plant development and physiology are strongly influenced by the light spectrum of the growth environment. The modulation of specific wavelengths affects a wide range of plant processes and also determine structural changes. The control light quality in the environment may promote several physiological, morphological and biochemical traits in the plant, such as gas exchanges, biomass production, pigment composition and antioxidant synthesis. In this work, we evaluate if appropriate light fertilisation protocols could improve Spinacia oleracea L. growth and quality regarding photosynthesis, biomass and bioactive compound production. Spinach seeds were germinated in a growth chamber and exposed to four different light quality treatments of 350 mol photons m-2 s-1: white light (WL), “pure” Red (R), Red-Blue (RB, 60% Red - 40% Blue), Red-Green-Cyan (RGC, 60% Red - 20% Green - 20% Cyan). Plants have been monitored until 100 days after sowing (DAS) and biometrical (leaf area, root and shoot biomass), physiological (gas exchanges and fluorescence emission) and biochemical (photosynthetic pigments, antioxidants, sugars and total protein content) traits were determined. Compared to WL and R treatments, the growth under RB induced the decrease of leaf area, a more compact plant size as well as higher photosynthetic and transpiration rates, likely due to the blue light stimulation on stomata opening. As additional valuable characteristics, the RB treatment determined an increase of carbohydrates and total chlorophylls as well as a reduction of phenolic compounds compared to the other treatments, increasing the palatability of leaves. The overall results confirm the light manipulation as a valuable tool to obtain favourable traits in plants.

In this paper we report results obtained in the fabrication and use of novel coded diffractive nano-optics that, beyond focusing, can perform new optical functions. In particular, the intensity of light in the space beyond the optical elements can be redistributed with almost complete freedom. These novel X-ray optical elements have been tested and found to perform multi-focusing in single or multiple focal planes and beam shaping of a generic monochromatic beam into a desired continuous geometrical pattern. Already available extreme ultraviolet and X-ray sources are suitable as ideal sources for such diffractive optical elements. Their new optical functions have been tested in differential interference contrast microscopy and we suggest their use also in maskless lithography and chemical vapour deposition induced by extreme ultraviolet and X-ray radiation.

Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are two multifactorial, heterogeneous and genetically complex neurodegenerative disorders. Despite massive research and drug development efforts, there are still no therapies that slow down or stop their progression. Several genes have been associated with both pathologies, suggesting that an as yet unknown common molecular pathway could exist. Mutations in genes related to neuroinflammation may be predisposing factors in these diseases. Coding and non-coding polymorphisms in genes expressed in microglia, including CD33 and TREM2, are risk factors and could be entry points for therapeutic intervention. Two SNPs in CD33 and one in TREM2 were described to be risk factors associated with Late Onset Alzheimer disease (LOAD). Specifically, CD33 SNPs rs3856444 and rs12459419 in minor alleles were found to confer strong protection while conferring elevated risk of LOAD in major alleles. These SNPs directly modulate the CD33 exon 2 splicing efficiency. In addition, the rare heterozygous missense variant rs75932628-T in TREM2 exon 2 was strongly associated with the ability of TREM2 to activate microglial cells. In order to assess the presence of these polymorphisms in an FTD cohort, we analyzed 216 Caucasians, mean age 60-85 years, diagnosed with LOAD, and 50 age-matched healthy controls. We used High Resolution Melting analysis (HRM) on genomic DNA from the whole blood of patients as a screen for mismatches. We sequenced the DNA from individuals with different melting curves using the Sanger method and used these results as a reference in our analysis. Our patients exhibited the coinheritance of SNPs rs12459419 and rs3865444, being heterozygous in 40%, homozygous for the major allele in 56.48% and homozygous for the minor allele in 3.7% of individuals. In addition, we identified a third SNP in CD33 exon 2, rs2455069, which belongs to a previously identified LD SNP block associated with an increased rate of cognitive decline. We found that all patients analyzed for SNP rs75932628 in the TREM2 gene are homozygous for the wild-type allele. However, some individuals are heterozygous for the nearby SNP rs143332484, which could be potentially associated with AD in our population. Further investigations are in progress to understand the mechanism of action of these two genes.

Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are two complex neurodegenerative disorders with associated several genes thus suggesting that a common molecular pathway could exist and is yet unknown. Despite massive research and drug development, there are still no therapies that slow down or stop their progression. Mutations in genes related to neuroinflammation, including CD33 and TREM2, may be risk factors and could be entry points for therapeutic intervention. Two CD33 SNPs and one in TREM2 were described to be predisposing factors to Late Onset Alzheimer disease (LOAD). In particular, CD33 SNPs rs3865444 and rs12459419 in minor alleles were found to confer strong protection while conferring elevated risk of LOAD in major alleles. These SNPs directly modulate CD33 exon 2 splicing efficiency. Moreover, the rare heterozygous missense variant rs75932628-T in TREM2 exon 2 was strongly associated with the capacity of TREM2 to activate microglial cells. In order to assess the presence of these polymorphisms in our cohort, we analyzed 216 Caucasians diagnosed with LOAD and 50 healthy controls. We performed High Resolution Melting analysis (HRM) on genomic DNA from whole blood of the patients and we sequenced by Sanger method individuals showing different melting curves and we used these results as reference in our analysis. Our patients exhibited the coinheritance of SNPs rs12459419 and rs3865444. In addition, we identified a third SNP in CD33 exon 2, rs2455069, which belongs to a previously identified LD SNP block associated with an increased rate of cognitive decline. We found that all patients analyzed for SNP rs75932628 in TREM2 gene are homozygous for the wild-type allele. However, some individuals are heterozygous for the nearby SNP rs143332484, which could be potentially associated with AD in our population. Further investigations are in progress to understand the mechanism of action of these two genes.

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by clinical and neuropathological heterogeneity and high genetic complexity. Granulin gene (GRN) is a major genetic determinant and Progranulin protein (PGRN) haploinsufficiency is the proposed disease mechanism. Patients with PGRN deficiency, show mainly ubiquitin-positive TAR DNA-binding protein 43 (TDP-43) aggregates in the brain, however the neurobiology of this protein remain still unclear. We collected and screened 256 FTD patients and 300 healthy, age-, sex- and geographic region-matched controls and sequenced all the coding exons of GRN and MAPT genes in patients with a familial history for dementia. We identified a rare GRN gene exon six deletion g10325_10331delCTGCTGT (relative to nt 1 in NG_007886.1), alias Cys157LysfsX97 in three autosomal dominant pedigrees of Southern Italian segregating FTD on three generations. We identified and analyzed the effect of this GRN mutation at transcriptional and translational levels and observed deficiency of the protein. With the goal to provide an efficient model system to dissect the molecular mechanisms of PGRN in pathway potentially involved in FTD-TDP43 proteinopathy, we generated by CRISPR-Cas9 a cellular model of PGRN deficiency. We silenced GRN gene in mouse embryonic stem cells (E14), then subjected wild-type and knock-out E14 cells to neuronal differentiation to have a mature neuronal phenotype lacking PGRN. With the hypothesis of an impairment of autophagic-lysosomal pathway in cases of PGRN deficiency, we performed, by quantitative RT-PCR, mRNA gene expression analysis of autophagy related genes. Preliminary results show a decrease of Beclin2 and LC3 genes in PGRN deficient cells compared to wild-type E14. Our findings support the role of GRN gene in the etiology of FTD and that PGRN insufficiency can predisposes to neurons degeneration. We can moreover speculate a role of PGRN in the regulation of autophagic-lysosomal pathway further analysis are in progress to confirm this hypothesis and to identify the connection with FTD onset.

Progranulin (PGRN) is genetically associated with frontotemporal dementia (FTD) but the neurobiology remains unclear. We performed genetic studies on 256 FTD patients and identified a rare exon six GRN deletion g10325_10331delCTGCTGT in three autosomal dominant Southern Italian pedigrees. Transcriptional and translational analysis demonstrated that FTD patients carrying this GRN mutation have a deficiency of the protein. To provide an efficient system to investigate the effects of PGRN depletion on neuronal cells, we generated a stable clone with PGRN deficiency by CRISPRCas9. To begin testing the hypothesis that patients with PGRN deficiency have an impaired autophagic-lysosomal pathway, we performed mRNA expression analysis of autophagy related genes. Preliminary results demonstrated decreased expression of autophagy-related genes Beclin2 and LC3 in GRN knock-out cells compared to wild-type cells. Our preliminary observations support the role of the GRN gene in the etiology of FTD and the hypothesis that PGRN insufficiency can predispose to neuron degeneration.

Progranulin (GRN) is genetically associated with frontotemporal dementia (FTD), with mutations present in 23% of patients with familial FTD. The neurobiology of progranulin (PGRN) is still unclear, although the proposed disease mechanism is linked to a deficiency of the protein. Furthermore, patients with PGRN deficiency express primarily ubiquitin-positive TAR DNA-binding protein 43 (TDP-43) aggregates in the brain. It is possible that misfolded proteins may aggregate similarly to prions, converting a native protein into a pathologic misfolded replicate able to initiate template-directed protein misfolding. We enrolled 256 FTD patients and 300 healthy age-, sex- and geographic region-matched controls and sequenced all the coding exons of GRN and MAPT genes in patients with a familial history for dementia. We identified a rare GRN gene exon six deletion, g10325_10331delCTGCTGT (relative to nt 1 in NG_007886.1), alias Cys157LysfsX97, in three autosomal dominant pedigrees in Southern Italy segregating FTD in three generations. Transcriptional and translational analysis of mRNA from WBC and plasma proteins from FTD patients carrying the mutation exhibited deficiency of the protein. We used mouse embryonic stem cells (E14) with the goal of generating a cell model using CRISPR-Cas9, to test regulatory functions and pathological mechanisms of PGRN in vitro. We designed single guide RNA for the GRN gene with high specific, on-target activity and derived pure cellular clones carrying homozygote GRN gene mutations causing protein deficiency. We subjected wild-type and knock-out E14 cells to neuronal differentiation, generating an efficient model system to dissect the molecular mechanisms of PGRN in pathways potentially involved in FTD-TDP43 proteinopathy. To test the hypothesis that PGRN deficiency results in an impairment of the autophagic-lysosomal pathway, we performed mRNA gene expression analysis of autophagy-related genes using quantitative RT-PCR. Preliminary results demonstrated a decrease of Beclin2 and LC3 genes in PGRN-deficient cells compared to wild-type E14. Our findings support the role of the GRN gene in the etiology of FTD and the hypothesis that PGRN insufficiency can be a predisposing factor in neuronal degeneration. We can also speculate that PGRN plays a role in the regulation of the autophagic-lysosomal pathway. Further analyses are in progress to confirm this hypothesis and to identify the connection with the onset of FTD.

Frontotemporal Dementia (FTD) is a neurodegenerative disorder characterized by clinical and neuropathological heterogeneity and high genetic complexity. Granulin gene (GRN) is an important predisposing factor for FTD and the proposed disease mechanism is deficiency of the protein. Progranulin (PGRN) is a secreted glycoprotein with several roles and expressed across a wide range of tissues including the brain, however, the neurobiology of this protein remains unclear. It is known that FTD patients with PGRN deficiency show ubiquitin-positive inclusions in the brain with accumulation of TDP-43 and do not show tau protein aggregates, altered protein conformations or aggregates trigger neuronal dysfunction and can spread to neighboring neurons. We previously studied three pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns. We identified in all the available patients in these three familial cases a rare GRN gene exon six deletion g10325_10331delCTGCTGT (relative to nt 1 in NG_007886.1), alias Cys157LysfsX97. We identified and analyzed the effect of the GRN mutation at transcriptional and translational levels revealing that this deletion lead to haploinsufficiency of the protein. Our findings provide further support for a previously proposed role for the GRN gene in the genetic etiology of FTD and its phenotypic variability. I am now presenting a neuronal cellular model generated by CRISPR-Cas9 for the study of mechanisms potentially involved in neuronal cell death following PGRN deficiency. I am testing the behave of TDP-43 aggregates and their spreading in this cellular model thus to analyze whether there are molecular changes in tight association with this mutation. It is my hypothesis that specific FTD pathological targets exist and my task is to first identify molecular defects and second develop strategies for the rescue of dysfunctional neurodegenerative phenotypes.

Context.—The role of pathologists' assistants (PAs) in terms of surgical and autopsy prosection has been well established; however, the role of PAs in areas beyond surgical and autopsy pathology, such as laboratory administration and management, education, and research, is not so well understood.Objective.—To determine the scope and extent of ancillary duties (value-added benefits) performed by PAs.Design.—A self-administered, electronic survey was disseminated to all members of the American Association of Pathologists' Assistants with fellowship status to analyze the ancillary duties PAs provide in laboratory administration and management, education, and research.Results.—Respondents were from 44 states and most had 6 or more years of experience in various work settings: community hospitals (50%), academic hospitals (30%), private pathology laboratories (15%), and “other” settings (5%). Most were involved in quality assurance programs (64.0%), laboratory accreditation inspections (56.2%), and a large percentage (44.4%) also had direct supervisory experience. Roughly 36% of respondents reported training residents in prosection skills in a clinical setting, while a small percentage reported teaching for-credit courses in a classroom setting (4.9%). The primary research responsibility was fresh tissue procurement for tumor banking (52.7%).Conclusions.—Pathologists' assistants currently are involved in ancillary duties beyond surgical and autopsy prosection. Our findings indicate that PAs have a desire to become more involved in these duties, and there is opportunity for pathologists to benefit further by using PAs to the full extent of their knowledge, skills, and interests.

Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity.

Research on psychopathy among incarcerated White males has consistently demonstrated deficits in emotion processing and response inhibition. Using the Psychopathy Checklist—Revised to classify participants as psychopathic or nonpsychopathic, this study examined the performance of incarcerated White females on two laboratory tasks: a lexical decision task used to assess emotion processing and a passive avoidance task used to assess response inhibition. Contrary to prediction, deficits in performance typically exhibited by psychopathic males were not exhibited by psychopathic females in this sample. Implications of these findings are discussed and an interpretation of the results in the context of the response modulation hypothesis is presented.

Research on psychopathy in women has generated equivocal laboratory findings. This study examined the performance of psychopathic women in 2 laboratory tasks designed to assess abnormal selective attention associated with response modulation deficits: a computerized picture-word (PW) task, and a picture-word Stroop (PW Stroop) task. Consistent with data from psychopathic men, women receiving high scores on the Psychopathy Checklist - Revised (Hare, 1991) displayed reduced Stroop interference on the PW and PW Stroop tasks. Results suggest that despite some differences in the expression of psychopathy across gender, psychopathic women are characterized by selective attention abnormalities predicted by the response modulation hypothesis and similar to those exhibited by psychopathic men.