Presenilin-2 in the cynomolgus monkey brain: investigation of age-related changes

Localization of presenilin-2 (PS-2), a transmembrane protein implicated in early onset familial Alzheimers disease, was examined in the brains of 30 cynomolgus monkeys aged 4 to 36 years. Anti-PS-2 antibody N20, which recognizes PS-2 amino acid residues 2–20, and anti-PS-2 antibody C20, which recognizes PS-2 amino acid residues 535–554, stained mainly the cytoplasm of large pyramidal neurons and large neurites. This finding was also confirmed by double immunohistochemical investigations using N20 or C20 and anti-NeuN antibody. In the brain of the oldest monkey, swollen neurites containing senile plaques were immunostained with C20, but not with N20. Western blot analyses of microsomal fractions isolated from the brains of three adult monkeys revealed that much less PS-2 was present compared to presenilin-1 (PS-1). Age-related assessment of PS-2 in brain homogenates from young and adult monkeys showed that PS-2 levels and PS-2 subcellular localization were unchanged with increasing age. Because PS-2 expression was much less robust than that of PS-1, we conclude that PS-2 mainly localizes to large neurons and does not show so drastic age-related changes as PS-1.     

Susceptibility to Helicobacter pylori infection: results of an epidemiological investigation among gastric cancer patients

The aim of this study was to identify the clinical, demographic, lifestyle factors and selected genetic polymorphisms that affect the susceptibility towards Helicobacter pylori (H. pylori) infection in gastric cancer patients. Histological confirmed gastric adenocarcinoma cases that underwent curative gastrectomy between 2002 and 2012 were included. Gastric biopsy samples were obtained to determine the H. pylori status, and further cagA status and vacA m and s genotypes by polymerase chain reaction. Patients were interviewed with structured questionnaires, and blood samples were collected for EPHX1, GSTM1, GSTT1, IL1B, IL1-RN, MTHFR and p53 genotyping. Proportions were compared in univariate analysis, while the relation between putative risk factors and H. pylori status and genotype were measured using logistic regression analysis. One hundred forty-nine gastric cancer patients were included, of which 78.5 % were H. pylori positive. Among positive patients 50 % were cagA+, 72.5 % vacA m1 and 80.7 % vacA s1. The presence of cagA was less frequent among vacA m1 (p = 0.031) and vacA s1 (p = 0.052) subtypes. The presence of father history for any cancer was a significant risk factor for H. pylori infection [adjusted odds ratio (OR) = 8.18, 95 % confidence interval (CI) 1.04–64.55]. EPHX1 exon 3 T > C (OR = 0.35, CI 95 % 0.13–0.94), IL1B-511 T > C (OR = 0.38, CI 95 % 0.15–0.97) and IL1-RN VNTR (OR = 0.19, CI 95 % 0.06–0.58) polymorphisms were protective towards H. pylori infection in the univariate analysis. Wine consumption was associated with higher risk of carrying the H. pylori vacA m1 virulent subtype (p = 0.034). Lastly, cardiovascular diseases were less common among cagA positive subjects (p = 0.023). Father history of any cancer is a risk factor for H. pylori infection. Polymorphisms in IL1B-511, IL1-RN and EPHX1 exon 3 genes might be protective towards H. pylori infection.     

The development and use of an immunoenzyme test system for detecting and the species identification of the monkey pox virus]

An enzyme immunoassay (EIA) system for the species-specific diagnosis of monkeypox, based on the use of monoclonal antibodies (McAb) to monkeypox virus, has been developed. Immunoglobulins, isolated from McAb-containing cultural and immune ascitic fluids, have been conjugated with horse-radish peroxidase and used as detector antibodies. For immunosorption, rabbit polyclonal antibodies to the vaccine virus have been used. The specificity and sensitivity of the EIA system thus obtained have been tested on animals and humans having monkeypox and confirmed by traditional diagnostic methods (the isolation of the virus on chick embryo chorioallantoic membranes and in cell culture).     

Bartonella henselae infection in British Columbia: evidence for an endemic disease among humans

Human bartonellosis in North America is mainly associated with Bartonella henselae, and the availability of laboratory diagnostic tools has significantly heightened awareness of the spectrum of human disease that is caused by this bacterium. We detail herein examples of illness in a pediatric population which serve to confirm that B. henselae-associated disease exists in British Columbia. Seroprevalence studies among asymptomatic adults and among children with symptomatic respiratory illness of other causation demonstrated that 36.8% and 18.5% of sera, respectively, had IFA-IgG titres > or = 1:256. IFA-IgG titres did not vary significantly whether B. henselae ATCC 49793 or a local wild-type B. henselae isolate were used as substrate. An assessment of IgM response was consistent with the proposal that endemic seroprevalence is a function of past rather than recent exposure. Both clinical and serological studies are concordant in providing evidence that B. henselae is endemic in British Columbia.     

Avian pox infection in an American green-winged teal (Anas crecca carolinensis) in Alaska.

Poxvirus infection was diagnosed on the basis of gross and microscopic appearance plus the presence of typical inclusion bodies in a juvenile American green-winged teal (Anas crecca carolinensis) in Alaska. This constitutes the first known report of avian pox in migratory ducks and the first report of poxvirus infection in wild birds in Alaska.     

Risk factors for outbreaks of SARS-CoV-2 infection at retirement homes in Ontario,Canada: a population-level cohort study

BACKGROUND:The epidemiology of SARS-CoV-2 infection in retirement homes (also known as assisted living facilities) is largely unknown. We examined the association between home-and community-level characteristics and the risk of outbreaks of SARS-CoV-2 infection in retirement homes since the beginning of the first wave of the COVID-19 pandemic.METHODS:We conducted a population-based, retrospective cohort study of licensed retirement homes in Ontario, Canada, from Mar. 1 to Dec. 18, 2020. Our primary outcome was an outbreak of SARS-CoV-2 infection (≥ 1 resident or staff case confirmed by validated nucleic acid amplification assay). We used time-dependent proportional hazards methods to model the associations between retirement home– and community-level characteristics and outbreaks of SARS-CoV-2 infection.RESULTS:Our cohort included all 770 licensed retirement homes in Ontario, which housed 56 491 residents. There were 273 (35.5%) retirement homes with 1 or more outbreaks of SARS-CoV-2 infection, involving 1944 (3.5%) residents and 1101 staff (3.0%). Cases of SARS-CoV-2 infection were distributed unevenly across retirement homes, with 2487 (81.7%) resident and staff cases occurring in 77 (10%) homes. The adjusted hazard of an outbreak of SARS-CoV-2 infection in a retirement home was positively associated with homes that had a large resident capacity, were co-located with a long-term care facility, were part of larger chains, offered many services onsite, saw increases in regional incidence of SARS-CoV-2 infection, and were located in a region with a higher community-level ethnic concentration.INTERPRETATION:Readily identifiable characteristics of retirement homes are independently associated with outbreaks of SARS-CoV-2 infection and can support risk identification and priority for vaccination.

Frail older adults living in congregate care settings have been at the centre of the COVID-19 pandemic in Canada and internationally.^1,2 Long-term care facilities — whose residents are the congregate living population most affected by COVID-19 — have been the subject of immense scientific and public interest during the pandemic.³ Retirement homes (often known as assisted living facilities) have received far less examination despite also housing many vulnerable older adults.^4–7 In contrast to long-term care facilities, retirement homes are private residential complexes that provide a range of supportive care and lifestyle services that are purchased out of pocket by residents or their families.⁸ Although residents of retirement homes access supportive care services, they are substantially less frail and dependent than residents of long-term care homes.⁵ Inconsistent regulation of these facilities throughout Canada and the United States has limited research into the epidemiology of SARS-CoV-2 infection in retirement homes.⁹There are 770 licensed retirement homes in Ontario, Canada’s most populous province, that house more than 50 000 older adults, a population size that approaches the number of Ontario residents of long-term care homes.¹⁰ Since the onset of the COVID-19 pandemic in Ontario, the number of positive cases and deaths in retirement homes has continued to grow. As of Apr. 11, 2021, retirement home residents accounted for about 8% of deaths from COVID-19 in Ontario (596/7552).¹¹ Outbreaks of SARS-CoV-2 infection surged in retirement homes during the first and second waves in Canada and the US,^11,12 and there has been limited examination in the literature beyond early reports of case surveillance.¹³We examined the association between home- and community-level characteristics and the risk of outbreaks of SARS-CoV-2 infection during the first wave of the COVID-19 epidemic in Ontario’s retirement homes. Consistent with our previous population-level work in Ontario long-term care homes,^2,14 we hypothesized that home size and regional incidence of SARS-CoV-2 infection would be associated with the risk of an outbreak.     

Endemic threshold results in an age-duration-structured population model for HIV infection

In this paper we consider an age-duration-structured population model for HIV infection in a homosexual community. First we investigate the invasion problem to establish the basic reproduction ratio R(0) for the HIV/AIDS epidemic by which we can state the threshold criteria: The disease can invade into the completely susceptible population if R(0)>1, whereas it cannot if R(0)<1. Subsequently, we examine existence and uniqueness of endemic steady states. We will show sufficient conditions for a backward or a forward bifurcation to occur when the basic reproduction ratio crosses unity. That is, in contrast with classical epidemic models, for our HIV model there could exist multiple endemic steady states even if R(0) is less than one. Finally, we show sufficient conditions for the local stability of the endemic steady states.     

格特隐球菌病暴发流行机制的研究进展

目前已证实, 格特隐球菌病可暴发流行。近10 年来, 在加拿大温哥华岛暴发的格特隐球菌病发病率显著高于其他地区, 且大部分感染者免疫力正常, 该致病菌已蔓延至周边地区。本文就格特隐球菌病暴发流行机制, 包括致病菌的分子流行病学分析、可能来源、毒力分析和播散机制进行综述。     

The apoplastic antioxidant system in Prunus: response to long-term plum pox virus infection

This work describes, for the first time, the changes taking place in the antioxidative system of the leaf apoplast in response to plum pox virus (PPV) in different Prunus species showing different susceptibilities to PPV. The presence of p-hydroxymercuribenzoic acid (pHMB)-sensitive ascorbate peroxidase (APX) (class I APX) and pHMB-insensitive APX (class III APX), superoxide dismutase (SOD), peroxidase (POX), NADH-POX, and polyphenoloxidase (PPO) was described in the apoplast from both peach and apricot leaves. PPV infection produced different changes in the antioxidant system of the leaf apoplast from the Prunus species, depending on their susceptibility to the virus. In leaves of the very susceptible peach cultivar GF305, PPV brought about an increase in class I APX, POX, NADH-POX, and PPO activities. In the susceptible apricot cultivar Real Fino, PPV infection produced a decrease in apoplastic POX and SOD activities, whereas a strong increase in PPO was observed. However, in the resistant apricot cultivar Stark Early Orange, a rise in class I APX as well as a strong increase in POX and SOD activities was noticed in the apoplastic compartment. Long-term PPV infection produced an oxidative stress in the apoplastic space from apricot and peach plants, as observed by the increase in H2O2 contents in this compartment. However, this increase was much higher in the PPV-susceptible plants than in the resistant apricot cultivar. Only in the PPV-susceptible apricot and peach plants was the increase in apoplastic H2O2 levels accompanied by an increase in electrolyte leakage. No changes in the electrolyte leakage were observed in the PPV-inoculated resistant apricot leaves, although a 42% increase in the apoplastic H2O2 levels was produced. Two-dimensional electrophoresis analyses revealed that the majority of the polypeptides in the apoplastic fluid had isoelectric points in the range of pI 4-6. The identification of proteins using MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) and peptide mass fingerprinting analyses showed the induction of a thaumatin-like protein as well as the decrease of mandelonitrile lyase in peach apoplast due to PPV infection. However, most of the selected polypeptides showed no homology with known proteins. This fact emphasizes that, at least in Prunus, most of the functions of the apoplastic space remain unknown. It is concluded that long-term PPV infection produced an oxidative stress in the leaf apoplast, contributing to the deleterious effects produced by PPV infection in leaves of inoculated, susceptible Prunus plants.     

Duplication of GTF2I results in separation anxiety in mice and humans

Duplication (dup7q11.23) and deletion (Williams syndrome) of chromosomal region 7q11.23 cause neurodevelopmental disorders with contrasting anxiety phenotypes. We found that 30% of 4- to 12-year-olds with dup7q11.23 but fewer than 5% of children with WS or in the general population met diagnostic criteria for a separation-anxiety disorder. To address the role of one commonly duplicated or deleted gene in separation anxiety, we compared mice that had varying numbers of Gtf2i copies. Relative to mouse pups with one or two Gtf2i copies, pups with additional Gtf2i copies showed significantly increased maternal separation-induced anxiety as measured by ultrasonic vocalizations. This study links the copy number of a single gene from 7q11.23 to separation anxiety in both mice and humans, highlighting the utility of mouse models in dissecting specific gene functions for genomic disorders that span many genes. This study also offers insight into molecular separation-anxiety pathways that might enable the development of targeted therapeutics.     

Inhalation efficacy of RFI-641 in an African green monkey model of RSV infection

Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73-1.34 PFU/ml (P-value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection.     

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans

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Transmission of Pneumocystis infection in humans

Is Pneumocystis pneumonia (PcP) a transmissible fungal disease? Does nosocomial PcP occur? Is there Pneumocystis transmission in the community? These questions, which could not be tackled before the 2000s, may at present be approached using either noninvasive detection methods or experimental transmission models. Represented by a unique entity (P.?carinii) for almost one century, the Pneumocystis genus was shown to contain several species, being P.?jirovecii the sole species identified in humans hitherto. Molecular methods combined with cross infection experiments revealed strong host specificity that precludes Pneumocystis inter-species transmission. In contrast, respiratory transmission between mammals of a same species is usually highly active, even between immunocompetent hosts. Other transmission ways could also exist. New data show that human being is the unique P.?jirovecii reservoir; it would constitute the sole infection source in both hospital and community.