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Marcus Aemilius Lepidus was one of three Roman legati sent to Greece in 201/200 b.c.e. and ended up confronting Philip V of Macedon at Abydus. Scholars have debated whether this young man was already a senator by 201 or had yet to become one. This paper argues that he had actually been a senator since 216, enrolled in Buteo’s extraordinary lectio of one hundred and seventy-seven new senators, after he had gained a corona ciuica and spolia ex hoste during the early stages of the Hannibalic War.

Valerius Antias, a 1st century BCE Roman annalist, has often been accused of extensive fabrications. John Rich has recently tried to restore Antias’ reputation, suggesting that he used senatus consulta, but has faced a serious roadblock: Antias’ account of the senatus consultum freeing the Greeks in 196, preserved in Livy, contained clauses absent from Polybius’ version and which, therefore, have been rejected by scholarship. In contrast, this paper systematically evaluates these Valerian clauses and argues for their veracity. This has serious implications for the idea that annalists like Antias, and ultimately Livy, accurately conveyed senatorial decrees from the Middle Republic.

Valerius Antias, a 1st century BCE Roman annalist, has often been accused of extensive fabrications. John Rich has recently tried to restore Antias’ reputation, suggesting that he used senatus consulta, but has faced a serious roadblock: Antias’ account of the senatus consultum freeing the Greeks in 196, preserved in Livy, contained clauses absent from Polybius’ version and which, therefore, have been rejected by scholarship. In contrast, this paper systematically evaluates these Valerian clauses and argues for their veracity. This has serious implications for the idea that annalists like Antias, and ultimately Livy, accurately conveyed senatorial decrees from the Middle Republic.

SARS-CoV-2 viral attachment and entry into host cells is mediated by a direct interaction between viral spike glycoproteins and membrane bound angiotensin-converting enzyme 2 (ACE2). The receptor binding motif (RBM), located within the S1 subunit of the spike protein, incorporates the majority of known ACE2 contact residues responsible for high affinity binding and associated virulence. Observation of existing crystal structures of the SARS-CoV-2 receptor binding domain (S RBD )–ACE2 interface, combined with peptide array screening, allowed us to define a series of linear native RBM-derived peptides that were selected as potential antiviral decoy sequences with the aim of directly binding ACE2 and attenuating viral cell entry. RBM1 (16mer): S 443 KVGGNYNYLYRLFRK 458 , RBM2A (25mer): E 484 GFNCYFPLQSYGFQPTNGVGYQPY 508 , RBM2B (20mer): F 456 NCYFPLQSYGFQPTNGVGY 505 and RBM2A-Sc (25mer): NYGLQGSPFGYQETPYPFCNFVQYG. Data from fluorescence polarisation experiments suggested direct binding between RBM peptides and ACE2, with binding affinities ranging from the high nM to low μM range (K d = 0.207–1.206 μM). However, the RBM peptides demonstrated only modest effects in preventing S RBD internalisation and showed no antiviral activity in a spike protein trimer neutralisation assay. The RBM peptides also failed to suppress S1-protein mediated inflammation in an endogenously expressing ACE2 human cell line. We conclude that linear native RBM-derived peptides are unable to outcompete viral spike protein for binding to ACE2 and therefore represent a suboptimal approach to inhibiting SARS-CoV-2 viral cell entry. These findings reinforce the notion that larger biologics (such as soluble ACE2, ‘miniproteins’, nanobodies and antibodies) are likely better suited as SARS-CoV-2 cell-entry inhibitors than short-sequence linear peptides.

Background Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder associated with long‐term, impairing symptoms of inattention and/or impulsivity/hyperactivity‐restlessness into adulthood and late‐life. Emerging epidemiological evidence suggests that ADHD is associated with an increased risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Furthermore, genetic predisposition to ADHD has been linked to cognitive decline and AD‐related pathophysiology. It is unclear whether AD risk in ADHD is driven by reduced brain resilience to the effects of AD pathophysiology (e.g., amyloid pathology) or shared risk factors that directly affect AD pathology (e.g., cardiovascular health). Pathways to AD have been principally tested in samples free from neurodevelopmental differences, making it impossible to know the applicability of commonly studied AD pathways in vulnerable groups. Moreover, studies of ADHD in AD have been hampered by reliance on electronic health records, which can present biased estimates of ADHD prevalence due to unclear diagnostic accuracy. Method To begin addressing these issues, we are conducting cognitive and AD biomarker assessments with 100 participants from the Pittsburgh ADHD Longitudinal Study (PALS), a cohort of individuals with rigorous diagnoses of ADHD in childhood. Participants are in their 40s, with 25/100 assessed to date, 19 ADHD and 6 nonADHD, Mage=44.5, 28% Black or multiple race, 24% women. We anticipate 50 assessments by 06/25. This research is studying feasibility of procedures in the larger PALS sample and gathering preliminary data about group differences in cognitive functioning pertinent to ADHD and AD risk and blood‐based biomarkers of AD, some of which are known to be altered in preclinical stages of the disease. Example cognitive tests are MoCA and Rey Auditory Verbal Learning Test–Immediate/Recall; example blood‐based biomarkers are plasma Ab42/40, tau (p‐tau181, 217), and inflammation‐related markers. Result We will report preliminary group comparisons, emphasizing effect sizes given interim study progress. Conclusion Understanding the association between rigorous, prospectively diagnosed ADHD and prevalent age‐related diseases, such as AD, is a pressing concern given the increased prevalence of ADHD in adulthood. Our research is beginning to address this need including demonstrating feasibility of measuring cognition and AD biomarkers in midlife adults with ADHD histories.

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder associated with long-term, impairing symptoms of inattention and/or impulsivity/hyperactivity-restlessness into adulthood and late-life. Emerging epidemiological evidence suggests that ADHD is associated with an increased risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Furthermore, genetic predisposition to ADHD has been linked to cognitive decline and AD-related pathophysiology. It is unclear whether AD risk in ADHD is driven by reduced brain resilience to the effects of AD pathophysiology (e.g., amyloid pathology) or shared risk factors that directly affect AD pathology (e.g., cardiovascular health). Pathways to AD have been principally tested in samples free from neurodevelopmental differences, making it impossible to know the applicability of commonly studied AD pathways in vulnerable groups. Moreover, studies of ADHD in AD have been hampered by reliance on electronic health records, which can present biased estimates of ADHD prevalence due to unclear diagnostic accuracy. To begin addressing these issues, we are conducting cognitive and AD biomarker assessments with 100 participants from the Pittsburgh ADHD Longitudinal Study (PALS), a cohort of individuals with rigorous diagnoses of ADHD in childhood. Participants are in their 40s, with 25/100 assessed to date, 19 ADHD and 6 nonADHD, M =44.5, 28% Black or multiple race, 24% women. We anticipate 50 assessments by 06/25. This research is studying feasibility of procedures in the larger PALS sample and gathering preliminary data about group differences in cognitive functioning pertinent to ADHD and AD risk and blood-based biomarkers of AD, some of which are known to be altered in preclinical stages of the disease. Example cognitive tests are MoCA and Rey Auditory Verbal Learning Test-Immediate/Recall; example blood-based biomarkers are plasma Ab42/40, tau (p-tau181, 217), and inflammation-related markers. We will report preliminary group comparisons, emphasizing effect sizes given interim study progress. Understanding the association between rigorous, prospectively diagnosed ADHD and prevalent age-related diseases, such as AD, is a pressing concern given the increased prevalence of ADHD in adulthood. Our research is beginning to address this need including demonstrating feasibility of measuring cognition and AD biomarkers in midlife adults with ADHD histories.

SARS-CoV-2 viral attachment and entry into host cells is mediated by a direct interaction between viral spike glycoproteins and membrane bound angiotensin-converting enzyme 2 (ACE2). The receptor binding motif (RBM), located within the S1 subunit of the spike protein, incorporates the majority of known ACE2 contact residues responsible for high affinity binding and associated virulence. Observation of existing crystal structures of the SARS-CoV-2 receptor binding domain (SRBD)–ACE2 interface, combined with peptide array screening, allowed us to define a series of linear native RBM-derived peptides that were selected as potential antiviral decoy sequences with the aim of directly binding ACE2 and attenuating viral cell entry. RBM1 (16mer): S443KVGGNYNYLYRLFRK458, RBM2A (25mer): E484GFNCYFPLQSYGFQPTNGVGYQPY508, RBM2B (20mer): F456NCYFPLQSYGFQPTNGVGY505 and RBM2A-Sc (25mer): NYGLQGSPFGYQETPYPFCNFVQYG. Data from fluorescence polarisation experiments suggested direct binding between RBM peptides and ACE2, with binding affinities ranging from the high nM to low μM range (Kd = 0.207–1.206 μM). However, the RBM peptides demonstrated only modest effects in preventing SRBD internalisation and showed no antiviral activity in a spike protein trimer neutralisation assay. The RBM peptides also failed to suppress S1-protein mediated inflammation in an endogenously expressing ACE2 human cell line. We conclude that linear native RBM-derived peptides are unable to outcompete viral spike protein for binding to ACE2 and therefore represent a suboptimal approach to inhibiting SARS-CoV-2 viral cell entry. These findings reinforce the notion that larger biologics (such as soluble ACE2, ‘miniproteins’, nanobodies and antibodies) are likely better suited as SARS-CoV-2 cell-entry inhibitors than short-sequence linear peptides.