Fight Against the Mandatory COVID-19 Immunity Passport on Twitter: Natural Language Processing Study.

BACKGROUND: To contain and curb the spread of COVID-19, the governments of countries around the world have used different strategies (lockdown, mandatory vaccination, immunity passports, voluntary social distancing, etc). OBJECTIVE: This study aims to examine the reactions produced by the public announcement of a binding political decision presented by the president of the French Republic, Emmanuel Macron, on July 12, 2021, which imposed vaccination on caregivers and an immunity passport on all French people to access restaurants, cinemas, bars, and so forth. METHODS: To measure these announcement reactions, 901,908 unique tweets posted on Twitter (Twitter Inc) between July 12 and August 11, 2021, were extracted. A neural network was constructed to examine the arguments of the tweets and to identify the types of arguments used by Twitter users. RESULTS: This study shows that in the debate about mandatory vaccination and immunity passports, mostly "con" arguments (399,803/847,725, 47%; χ26=952.8; P<.001) and "scientific" arguments (317,156/803,583, 39%; χ26=5006.8; P<.001) were used. CONCLUSIONS: This study shows that during July and August 2021, social events permeating the public sphere and discussions about mandatory vaccination and immunity passports collided on Twitter. Moreover, a political decision based on scientific arguments led citizens to challenge it using pseudoscientific arguments contesting the effectiveness of vaccination and the validity of these political decisions.

Redox partner recognition and selectivity of cytochrome P450lin (CYP111A1).

The strict requirement of cytochrome P450cam for its native ferredoxin redox partner, putidaredoxin (Pdx), is not exhibited by any other known cytochrome P450 (CYP) system and the molecular details of redox partner selectivity are still not completely understood. We therefore examined the selectivity of a related Pseudomonas cytochrome P450, P450lin, by testing its activity with non-native redox partners. We found that P450lin could utilize Arx, the native redox partner of CYP101D1, to enable turnover of its substrate, linalool, while Pdx showed limited activity. Arx exhibited a higher sequence similarity to P450lins native redox partner, linredoxin (Ldx) than Pdx, including several residues that are believed to be at the interface of the two proteins, based on the P450cam-Pdx complex structure. We therefore mutated Pdx to resemble Ldx and Arx and found that a double mutant, D38L/∆106, displayed higher activity than Arx. In addition, Pdx D38L/∆106 does not induce a low-spin shift in linalool bound P450lin but does destabilize the P450lin-oxycomplex. Together our results suggest that P450lin and its redox partners may form a similar interface to P450cam-Pdx, but the interactions that allow for productive turnover are different.

Predicting the environmental fates of emerging contaminants: Synergistic effects in ozone reactions of nitrogen-containing alkenes.

While nitro and amino alkenes are common in pharmaceuticals, pesticides, and munitions, their environmental fates are not well known. Ozone is a ubiquitous atmospheric oxidant for alkenes, but the synergistic effects of nitrogen-containing groups on the reactions have not been measured. The kinetics and products of ozonolysis of a series of model compounds with different combinations of these functional groups have been measured in the condensed phase using stopped-flow and mass spectrometry methods. Rate constants span about six orders of magnitude with activation energies ranging from 4.3 to 28.2 kJ mol-1. Vinyl nitro groups substantially decrease the reactivity, while amino groups have the opposite effect. The site of the initial ozone attack is highly structure dependent, consistent with local ionization energy calculations. The reaction of the neonicotinoid pesticide nitenpyram, which forms toxic N-nitroso compounds, was consistent with model compounds, confirming the utility of model compounds for assessing environmental fates of these emerging contaminants.

Cooperative Substrate Binding Controls Catalysis in Bacterial Cytochrome P450terp (CYP108A1).

Despite being one of the most well-studied aspects of cytochrome P450 chemistry, important questions remain regarding the nature and ubiquity of allosteric regulation of catalysis. The crystal structure of a bacterial P450, P450terp, in the presence of substrate reveals two binding sites, one above the heme in position for regioselective hydroxylation and another in the substrate access channel. Unlike many bacterial P450s, P450terp does not exhibit an open to closed conformational change when substrate binds; instead, P450terp uses the second substrate molecule to hold the first substrate molecule in position for catalysis. Spectral titrations clearly show that substrate binding to P450terp is cooperative with a Hill coefficient of 1.4 and is supported by isothermal titration calorimetry. The importance of the allosteric site was explored by a series of mutations that weaken the second site and that help hold the first substrate in position for proper catalysis. We further measured the coupling efficiency of both the wild-type (WT) enzyme and the mutant enzymes. While the WT enzyme exhibits 97% efficiency, each of the variants showed lower catalytic efficiency. Additionally, the variants show decreased spin shifts upon binding of substrate. These results are the first clear example of positive homotropic allostery in a class 1 bacterial P450 with its natural substrate. Combined with our recent results from P450cam showing complex substrate allostery and conformational dynamics, our present study with P450terp indicates that bacterial P450s may not be as simple as once thought and share complex substrate binding properties usually associated with only mammalian P450s.

Structural Insights on the Conversion of Cytochrome P450 to P420.

A characteristic feature of cytochromes P450* is that the complex formed between the ferrous heme iron and carbon monoxide generates an intense absorption band at 450 nm. This unique feature of P450s is due to the proximal thiolate Cys ligand coordinated to the heme iron. Various harsh treatments shift this band to 420 nm, thereby giving P420 which is most often associated with an inactive form of the enzyme. Various explanations have been put forward to explain the P450-to-P420 change ranging from protonation of the Cys heme ligand, displacement of the Cys ligand, or replacement of the Cys ligand with His. There are two crystal structures of the well-studied cytochrome P450cam that have a high fraction of P420. In one, P450cam is cross-linked to its redox partner, putidaredoxin (Pdx), and the second is P450cam crystallized in the absence of substrate. In both of these structures, a significant part of the substrate pocket is disordered and the poor quality of the electron density for the substrate indicates substantial disorder. However, in both structures there is no detectable change in the Cys-iron ligation or surrounding structure. These results indicate that the P450-to-P420 switch is due primarily to an opening and disordering around the substrate binding pocket and not ligand displacement or ligand swapping. Since it remains a possibility that ligand swapping could be responsible for P420 in some cases, we mutated to Gln the 3 His residues (352, 355, and 361) close enough to the proximal side of the heme that could possibly serve as heme ligands. The triple variant forms P420 which indicates that swapping Cys for His is not a requirement for the P450-to-P420 switch.

Barriers, beliefs, and practices regarding hygiene and vaccination among the homeless during a hepatitis A outbreak in Detroit, MI.

Appropriate hygiene practices and vaccine acceptance are key factors impacting the health of homeless individuals. A recent outbreak of hepatitis A in Michigan, especially impacting Detroit, prompted us to investigate the practices and attitudes of Detroit's homeless population toward hygiene measures and vaccinations, as well as barriers to such resources. We developed a questionnaire as a means to collect our data, and participants were interviewed at shelters and soup kitchens. While the majority of participants adhered to healthy hygiene practices, approximately 89% reported barriers to accessing public showers. More than half the participants (64%) reported receiving their hepatitis A vaccine prior to the study, while 23% reported previously refusing or hesitating to receive vaccinations. Despite an overall favorable adherence to hygiene practices, substantial barriers are yet to be overcome. Moreover, active measures should be taken to establish higher levels of trust between providers and the homeless to encourage vaccine acceptance.

History of cerebral localization and the emigration plight of three neuroscience giants from Nazi Germany: Josef Gerstmann, Adolf Wallenberg, and Franz Josef Kallmann.

The Nazi regime held power for well over a decade in Germany and were steadfast in their anti-Semitic agenda. Among the massive cohort of immigrants to America were approximately 5056 Jewish physicians, including several highly esteemed neurologists and neuroscientists of the time. Emigrating to a new world proved difficult and provided new challenges by way of language barriers, roadblocks in medical careers, and problems integrating into an alien system of medical training and clinical practice. In this article, the authors examine the tumultuous and accomplished lives of three Jewish German and Austrian neurologists and neuroscientists during the time of the Third Reich who shaped the foundations of neuroanatomy and neuropsychology: Josef Gerstmann, Adolf Wallenberg, and Franz Josef Kallmann. The authors first examine the successful careers of these individuals in Germany and Austria prior to the Third Reich, followed by their journeys to and lives in the United States, to demonstrate the challenges an émigré physician faces for career opportunities and a chance at a new life. This account culminates in a description of these scientists' eponymous syndromes.Although their stories are a testimony to the struggles in Nazi Germany, there are intriguing and notable differences in their ages, ideologies, and religious beliefs, which highlight a spectrum of unique circumstances that impacted their success in the United States. Furthermore, in this account the authors bring to light the original syndromic descriptions: Gerstmann discovered contralateral agraphia and acalculia, right-left confusion, and finger agnosia in patients with dominant angular gyrus damage; Wallenberg described a constellation of symptoms in a patient with stenosis of the posterior inferior cerebellar artery; and Kallmann identified an association between hypogonadotropic hypogonadism and anosmia based on family studies. The article also highlights the unresolved confusions and international controversies about these syndromic descriptions. Still, these unique cerebral syndromes continue to fascinate neurologists and neurosurgeons across the world, from residents in training to practicing clinicians and neuroscientists alike.

Self- and Informant Ratings of Executive Functioning After Mild Traumatic Brain Injury.

OBJECTIVE: To determine correlates of self- and informant reports on a standardized rating of executive functioning in persons with mild traumatic brain injury. SETTING: Outpatient clinic at a rehabilitation hospital. PARTICIPANTS: One hundred referred persons who met criteria for mild traumatic brain injury (ie, time to follow commands <30 minutes, posttraumatic amnesia <24 hours, and Glasgow Coma Scale score >12). DESIGN: Retrospective case series review. MAIN MEASURES: Participants and informants completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) during outpatient neuropsychological evaluations within 30 to 360 days postinjury. RESULTS: Participant and informant BRIEF-A ratings were strongly correlated, but participants rated themselves as worse than informants did. Regression analysis revealed that higher levels of education and presence of intracranial neuroimaging findings were associated with better BRIEF-A ratings whereas worse BRIEF-A ratings were associated with longer time since injury and prior psychiatric treatment. BRIEF-A ratings were not correlated with laboratory measures of executive functioning. CONCLUSIONS: Subjective perceptions of executive dysfunction during the first year after mild TBI are driven primarily by premorbid factors and do not reflect acquired cerebral impairment.