Mutators in SACCHAROMYCES CEREVISIAE: MUT1–1, MUT1–2 and MUT2–1

The purpose of this study was to characterize two mutator stocks of yeast which were induced and selected on the basis of high spontaneous reversion rates of the suppressible "ochre" nonsense allele lys1-1. In the mutator stock VA-3, a single mutation, designated mut1-1, is responsible for the increase in the reversion rate of the ochre alleles lys1-1 and arg4-17. In stock VA-105, there are two separate mutator mutations. Tetrad analysis data showed these two loci are loosely linked. Based on complementation data, one of these mutations is at the same locus as mut1-1 and designated mut1-2. The second mutator of stock VA-105 was designated mut2-1. All three mutators are recessive. Both mut1-1 and mut1-2 give a high mutation rate for ochre nonsense suppressor (SUP) loci, but not for the ochre nonsense alleles. On the contrary, the mutation rates of the ochre alleles are greatly reduced. With the mutant mut2-1 there were mutations at both the lys1-1 site and its suppressors; mut2-1 is as effective as mut1-2 but not as effective as mut1-1 in inducing reversions of a missense mutant, his1-7. Neither mut1-1, mut1-2 nor mut2-1 were effective in inducing reversions of a putative frameshift mutation, hom3-10, or in inducing forward mutations to canavanine resistance.     

Footprints of SARS-CoV-2 genome diversity in Pakistan, 2020–2021

The rapid spread of SARS-CoV-2 has significantly impacted the worldwide health system. The SARS-CoV-2 currently bears a remarkably low genetic diversity even though it carries one of the largest RNA genomes among viruses (Rausch et al., 2020). However, the coronaviruses harbor the capability of undergoing recombination at a high rate which can lead to the emergence of novel viral derivatives (Rausch et al., 2020; Gribble et al., 2021). This in turn requires not only global surveillance of SARS-CoV-2 genome in various countries but also careful scrutiny in animal genomic reservoirs. Conventionally, RNA viruses evolve with a high mutation rate, however, the presence of ExoN ribonuclease in SARS-CoV-2 genome has made its case different from other viral species (Gribble et al., 2021). The variables of natural selection which potentially drift the SARS-CoV-2 evolutionary dynamics can be recorded by analyzing deposited sequence genomes for its fitness, transmissibility potential, and pathogenicity (Rouchka et al., 2020). This can potentially provide a way to draw a holistic picture at a national level, while simultaneously providing a comparative overview with worldwide sequences.     

Trends in Cancer Incidence in Maputo,Mozambique, 1991–2008

Background

Very limited information is available regarding the incidence of cancer in sub-Saharan Africa. We analyzed changes in cancer patterns from 1991 to 2008 in Maputo (Mozambique).

Methods

We calculated the rates of incidence of different cancer sites by sex in the 5-year age-group of the population of Maputo city as well as age-standardized rates (ASRs) and average annual percentage changes (AAPC).

Results

Over the 18-year study period a total of 12,674 cases of cancer (56.9% females) were registered with an overall increase in the risk of cancer in both sexes. In males, the most common cancers were those of the prostate, Kaposi sarcoma (KS) and the liver. Prostate cancer showed the most dramatic increase over the whole study period (AAPC +11.3%; 95% CI: 9.7–13.0), with an ASR of 61.7 per 10⁵ in 2003–2008. In females, the most frequent cancers were of the uterine cervix, the breast and KS, with the former increasing along the whole study period (AAPC + 4.7%; 95% CI: 3.4–6) with an ASR of 62.0 per 10⁵ in 2003–2008 as well as breast cancer (AAPC +6.5%; 95%CI: 4.3–8.7).

Conclusions

Overall, the risk of cancer rose in both sexes during the study period, particularly among cancers associated with westernization of lifestyles (prostate, breast), combined with increasingly rising incidences or limited changes in cancers associated with infection and poverty (uterine cervix, liver). Moreover, the burden of AIDS-associated cancers has shown a marked increase.     

Grandmothering in Cambridgeshire, 1770–1861

The effects of grandparent survival on child survival and mean interbirth interval, both independent of and relative to parent survival, were investigated in a historical population. Families for the data set were reconstituted from the parish and census records of Cambridgeshire, 1770–1861. In a logistic regression analysis, only the mother’s and the maternal grandmother’s survival were found to be significant predictors of child survival. Maternal grandmother’s survival was found to influence child survival both via maternal survival and independent of maternal survival. Grandparent survival was not found to influence mean interbirth interval. These findings are reviewed with respect to other studies of grandmothering, the Grandmother Hypothesis, and the evolutionary significance of human female postreproductive lifespan. Gillian Ragsdale is a postgraduate student at the Leverhulme Centre for Human Evolution Studies (LCHES), Cambridge University, UK, currently investigating the evolution of human social cognition. She was originally a molecular geneticist, and subsisted through the intervening years in educational publishing.     

Trends in schistosomiasis-related mortality in Brazil, 2000–2011

Schistosomiasis is an important public health problem, with high morbidity and mortality in endemic countries. We analysed the epidemiological characteristics and time trends of schistosomiasis-related mortality in Brazil. We performed a nationwide study based on official mortality data obtained from the Brazilian Mortality Information System. We included all deaths in Brazil between 2000 and 2011, in which schistosomiasis was mentioned on the death certificate as an underlying or associated cause of death (multiple causes of death). We calculated crude and age-adjusted mortality rates (per 100,000 inhabitants), and proportional mortality rates. Trends over time were assessed using joinpoint regression models. Over the 12-year study period, 12,491,280 deaths were recorded in Brazil. Schistosomiasis was mentioned in 8,756 deaths, including in 6,319 (72.2%) as an underlying cause and in 2,437 (27.8%) as an associated cause. The average annual age-adjusted mortality rate was 0.49 deaths/100,000 inhabitants (95% confidence interval: 0.46–0.52) and proportional mortality rate was 0.070% (95% confidence interval: 0.069–0.072). Males (0.53 deaths/100,000 inhabitants), those aged ⩾70 years (3.41 deaths/100,000 inhabitants), those of brown race/colour (0.44 deaths/100,000 inhabitants), and residents in the Northeast region of Brazil (1.19 deaths/100,000 inhabitants) had the highest schistosomiasis-related death rates. Age-adjusted mortality rates showed a significant decrease at a national level (Annual Percent Change: −2.8%; 95% confidence interval: −4.2 to −2.4) during the studied period. We observed decreasing mortality rates in the Northeast (Annual Percent Change: −2.5%; 95% confidence interval: −4.2 to −0.8), Southeast (Annual Percent Change: −2.2%; 95% confidence interval: −3.6 to −0.9), and Central-West (Annual Percent Change: −7.9%; 95% confidence interval: −11.3 to −4.3) regions, while the rates remained stable in the North and South regions. Despite the reduced mortality, schistosomiasis is still a neglected cause of death in Brazil, with considerable regional differences. Sustainable control measures should focus on increased coverage, and intensified and tailored control measures, to prevent the occurrence of severe forms of schistosomiasis and associated deaths.     

Mitochondrial GTPase mitofusin 2 mutation in Charcot–Marie–Tooth neuropathy type 2A

Charcot–Marie–Tooth disease (CMT) has been classified into two types, CMT1 and CMT2, demyelinating and axonal forms, respectively. CMT2 has been further subdivided into eight groups by linkage studies. CMT2A is linked to chromosome 1p35–p36 and mutation in the kinesin family member 1B-ß (KIF1B) gene had been reported in one pedigree. However, no mutation in KIF1B was detected in other pedigrees with CMT2A and the mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) gene were recently detected in those pedigrees. MFN2, a mitochondrial transmembrane GTPase, regulates the mitochondrial network architecture by fusion of mitochondria. We studied MFN2 in 81 Japanese patients with axonal or unclassified CMT and detected seven mutations in seven unrelated patients. Six of them were novel and one of them was a de novo mutation. Most mutations locate within or immediately upstream of the GTPase domain or within two coiled-coil domains, which are critical for the functioning or mitochondrial targeting of MFN2. Formation of a mitochondrial network would be required to maintain the functional peripheral nerve axon.     

Distribution and pollution evaluation of fluoride in a soil–water–plant system in Shihezi,Xinjiang, China

Fluoride (F) pollution is a serious environmental problem in some areas of China, but it has yet to be reported in a soil–water–plant system in Shihezi, Xinjiang. This study was undertaken to investigate the distribution and migration rule of F in soil, water, and plants, and to evaluate F pollution of soil. Results showed that the average concentration of total F (T-F) in the topsoil in the northwest, north, and southeast of Shihezi was higher than the national average T-F (478 mg/kg), while it was lower in southwest. The highest T-F contents of the soil profile were detected in the depth of 20 cm. The F content in groundwater in the northwest region was higher than the GB/T 14848–93 (1.0 mg/L), whereas the F contents in other water samples were within the standard. The F contents (1.75?2.81 mg/kg) in plant leaves were higher than the food limits (1.0 mg/kg). The obtained comprehensive pollution index of the soil was 1.86, which means a mild concentration of F in Shihezi. This research has reference value for the study of F pollution and comprehensive control in the northwest oasis with the typical arid and saline conditions.     

Influenza in Outpatient ILI Case-Patients in National Hospital-Based Surveillance,Bangladesh, 2007–2008

Background

Recent population-based estimates in a Dhaka low-income community suggest that influenza was prevalent among children. To explore the epidemiology and seasonality of influenza throughout the country and among all age groups, we established nationally representative hospital-based surveillance necessary to guide influenza prevention and control efforts.

Methodolgy/Principal Findings

We conducted influenza-like illness and severe acute respiratory illness sentinel surveillance in 12 hospitals across Bangladesh during May 2007–December 2008. We collected specimens from 3,699 patients, 385 (10%) which were influenza positive by real time RT-PCR. Among the sample-positive patients, 192 (51%) were type A and 188 (49%) were type B. Hemagglutinin subtyping of type A viruses detected 137 (71%) A/H1 and 55 (29%) A/H3, but no A/H5 or other novel influenza strains. The frequency of influenza cases was highest among children aged under 5 years (44%), while the proportions of laboratory confirmed cases was highest among participants aged 11–15 (18%). We applied kriging, a geo-statistical technique, to explore the spatial and temporal spread of influenza and found that, during 2008, influenza was first identified in large port cities and then gradually spread to other parts of the country. We identified a distinct influenza peak during the rainy season (May–September).

Conclusions/Significance

Our surveillance data confirms that influenza is prevalent throughout Bangladesh, affecting a wide range of ages and causing considerable morbidity and hospital care. A unimodal influenza seasonality may allow Bangladesh to time annual influenza prevention messages and vaccination campaigns to reduce the national influenza burden. To scale-up such national interventions, we need to quantify the national rates of influenza and the economic burden associated with this disease through further studies.     

Surfactin-Induced Apoptosis Through ROS–ERS–Ca2+-ERK Pathways in HepG2 Cells

Although surfactin is able to inhibit cancer cell proliferation and to induce cancer cell apoptosis, the molecular mechanism responsible for this process remain elusive. In this study, the signaling network underlying the apoptosis of human hepatoma (HepG2) cells induced by surfactin was investigated. It is found that the reaction oxygen species (ROS) production and intracellular calcium ([Ca²⁺]_i) accumulation are both induced HepG2 cells apoptosis. The [Ca²⁺]_i exaltation was partly depended on the Ca²⁺ release from inositol 1,4,5-trisphosphate (IP3) and ryanodine (Ry) receptors channels, which both triggered endoplasmic reticulum stress (ERS). The results showed that surfactin induced the ROS production and ROS production led to ERS. The occurrence of ERS increased the [Ca²⁺]_i level and the processes associated with blocking extracellular signal-regulated kinase (ERK) pathway. According to a comprehensive review of all the evidence, it is concluded that surfactin induces apoptosis of HepG2 cells through a ROS–ERS–Ca²⁺ mediated ERK pathway.     

Estimating Influenza Deaths in Canada, 1992–2009

Background

Poisson regression modelling has been widely used to estimate the disease burden attributable to influenza, though not without concerns that some of the excess burden could be due to other causes. This study aims to provide annual estimates of the mortality and hospitalization burden attributable to both seasonal influenza and the 2009 A/H1N1 pandemic influenza for Canada, and to discuss issues related to the reliability of these estimates.

Methods

Weekly time-series for all-cause mortality and regression models were used to estimate the number of deaths in Canada attributable to influenza from September 1992 to December 2009. To assess their robustness, the annual estimates derived from different parameterizations of the regression model for all-cause mortality were compared. In addition, the association between the annual estimates for mortality and hospitalization by age group, underlying cause of death or primary reason for admission and discharge status is discussed.

Results

The crude influenza-attributed mortality rate based on all-cause mortality and averaged over 17 influenza seasons prior to the 2009 A/H1N1 pandemic was 11.3 (95%CI, 10.5 - 12.1) deaths per 100 000 population per year, or an average of 3,500 (95%CI, 3,200 - 3,700) deaths per year attributable to seasonal influenza. The estimated annual rates ranged from undetectable at the ecological level to more than 6000 deaths per year over the three A/Sydney seasons. In comparison, we attributed an estimated 740 deaths (95%CI, 350–1500) to A(H1N1)pdm09. Annual estimates from different model parameterizations were strongly correlated, as were estimates for mortality and morbidity; the higher A(H1N1)pdm09 burden in younger age groups was the most notable exception.

Interpretation

With the exception of some of the Serfling models, differences in the ecological estimates of the disease burden attributable to influenza were small in comparison to the variation in disease burden from one season to another.     

Autochthonous Leptospirosis in South-East Austria, 2004–2012

Background

Leptospirosis is one of the world’s mostly spread zoonoses causing acute fever. Over years, leptospirosis has been reported to occur rarely in Austria and Germany (annual incidence of 0.06/100,000 in Germany). Only imported cases have been on the increase. Objectives of this case-series study were to retrospectively assess epidemiologic and clinical characteristics of leptospirosis illnesses in South-East Austria, to describe risk exposures for autochthonous infections, and to compare patients with imported versus autochthonous infection.

Methodology/Principal Findings

During the 9-year period between 2004 and 2012, 127 adult patients (49 females, 78 males) who tested positive by rapid point-of-care test for Leptospira-specific IgM (Leptocheck®) were identified through electronic hospital databases. Follow-up telephone interviews were conducted with 82 patients. A total of 114 (89.8%) of the 127 patients enrolled had acquired leptospirosis within Austria and 13 (10.2%) had potentially imported infections. Most autochthonous cases were diagnosed during the months of June and July, whereas fewest were diagnosed during the winter months. Exposure to rodents, recreational activities in woods or wet areas, gardening, cleaning of basements or huts were the most common risk exposures found in autochthonous infection. Serogroups Australis (n = 23), Sejroe (n = 22), and Icterohaemorrhagiae (n = 11) were identified most frequently by MAT testing in autochthonous infections. Patients with imported leptospirosis were significantly younger, less likely to be icteric and had significantly lower liver transaminase levels (p = 0.004) than those with autochthonous infections.

Conclusions/Significance

Leptospirosis is endemic in South-East Austria. In contrast to reports from other countries we found a relatively high proportion of leptospirosis cases to be female (39% vs. ∼10%), likely the result of differing risk exposures for South-East Austria.     

Sources of Mortality in Bald Eagles in Michigan, 1986–2017

As bald eagle populations recover, defining major sources of mortality provides managers important information to develop management plans and mitigation efforts. We obtained data from necropsies on 1,490 dead bald eagles (Haliaeetus leucocephalus) collected in Michigan, USA, conducted from 1986 to 2017 to determine causes of death (COD). Trauma and poisoning were the most common primary COD categories, followed by disease. Within trauma and poisoning, vehicular trauma (n = 532) and lead poisoning (n = 176) were the leading COD subcategories, respectively. Females comprised a greater number of carcasses for most COD diagnoses. The proportion of trauma and poisoning CODs significantly increased in the last few years of the study in comparison to a select few years at the beginning. Trauma CODs were greater in autumn months during whitetail deer (Odocoileus virginianus) breeding and hunting seasons and in February, when aquatic foraging is unavailable and eagles are likely forced to scavenge along roadsides. Poisoning CODs were greatest in late winter and early spring months, when deer carcasses containing lead ammunition, which are preserved by the cold weather, also become a supplemental food source. The major infectious disease CODs, West Nile virus and botulism (Clostridium botulinum type E), were more prevalent during summer months. We recommend moving road-killed carcasses, especially white-tailed deer, from the main thoroughfare to the back of the right-of-way, and the transition from lead ammunition and fishing tackle to non-toxic alternatives to decrease these main anthropogenic sources of mortality for bald eagles, and other scavenger species. © 2020 The Wildlife Society.     

Changes in breastfeeding initiation and duration in Peru, 1977–1986

Abstract

Both breastfeeding initiation and duration increased in Peru during 1977–86. Although one would have expected that the average incidence and duration of breastfeeding would have declined as a result of changes in population characteristics, the potential for an overall decline was more than overcome by changes in behavior. A net increase in initiation and duration is shown for all subgroups of interest. The largest absolute increases are documented for children who, in 1977, were the least likely to be breastfed and who were breastfed for the shortest durations.     

Optical Magnetic Resonances in Subwavelength Ag–MgF2–Ag Grating Structures

Optical magnetic responses were demonstrated in subwavelength Ag–MgF₂–Ag grating structures for transverse magnetic-polarized light. The subwavelength Ag–MgF₂–Ag grating structures were fabricated using e-beam lithography followed by a lift-off process. By fixing the Ag–MgF₂–Ag strip dimension, the effect of the stripe width on the magnetic resonances was compared for two different grating pitches. With further reduced grating pitch, we pushed the optical magnetic resonances to near UV (deep blue). Numerical simulations confirmed our experimental observations and were in good agreement with the experimental results.     

Estimated HIV Incidence in California, 2006–2009

Introduction

Accurate estimates of HIV incidence are crucial for prioritizing, targeting, and evaluating HIV prevention efforts. Using the methodology the CDC used to estimate national HIV incidence, we estimated HIV incidence in Los Angeles County (LAC), San Francisco (SF), and California’s remaining counties.

Methods

We estimated new HIV infections in 2006–2009 among adults and adolescents in LAC, SF and the remaining California counties using the Serologic Testing Algorithm for Recent Seroconversion (STARHS). STARHS methodology uses the BED HIV-1 capture enzyme immunoassay to determine recent HIV infections by testing remnant serum from persons newly diagnosed with HIV. A population-based incidence estimate is calculated using HIV testing data from newly diagnosed cases and imputing for persons unaware of their HIV infection.

Results

For years 2007–2009, respectively, we estimated new infections in LAC to be 2426 (95% CI 1871–2982), 1669 (CI 1309–2029) and 1898 (CI 1452–2344) (p<0.01); in SF for 2006–2009, 492 (CI 327–657), 490 (CI 335–646), 458 (CI 342–574) and 367 (CI 261–473) (p = 0.14); and in the remaining California counties in 2008–2009, 2526 (CI 1688–3364) and 2993 (CI 2141–3846) respectively. HIV infection rates among men who have sex with men (MSM) in LAC were 100 times higher than other risk populations; the SF MSM rate was 3 to 18 times higher than other demographic groups. In LAC, incidence rates among African-Americans were twice those of whites and Latinos; persons 40 years or older had lower rates of infection than younger persons.

Discussion

We report the first HIV incidence estimates for California, highlighting geographic disparities in HIV incidence and confirming national findings that MSM and African-Americans are disproportionately impacted by HIV. HIV incidence estimates can and should be used to target prevention efforts towards populations at highest risk of acquiring new HIV infections, focusing on geographic, racial and risk group disparities.     

Fatal mushroom poisoning in Barcelona, 1986–1988

In 1986–88, 46 poisonings (4 of which were fatal) caused by amatoxin mushroom were reported. The fatalities were males aged between 7 and 65 years. They all had gastrointestinal symptoms and three of the patients died of acute hepatic insufficiency. The fourth died as a result of an intestinal perforation. The clinical and pathological alterations are compared with the findings of other authors.     

Measles Case Fatality Rate in Bihar,India, 2011–12

Background

Updated estimates of measles case fatality rates (CFR) are critical for monitoring progress towards measles elimination goals. India accounted for 36% of total measles deaths occurred globally in 2011. We conducted a retrospective cohort study to estimate measles CFR and identify the risk factors for measles death in Bihar–one of the north Indian states historically known for its low vaccination coverage.

Methods

We systematically selected 16 of the 31 laboratory-confirmed measles outbreaks occurring in Bihar during 1 October 2011 to 30 April 2012. All households of the villages/urban localities affected by these outbreaks were visited to identify measles cases and deaths. We calculated CFR and used multivariate analysis to identify risk factors for measles death.

Results

The survey found 3670 measles cases and 28 deaths (CFR: 0.78, 95% confidence interval: 0.47–1.30). CFR was higher among under-five children (1.22%) and children belonging to scheduled castes/tribes (SC/ST, 1.72%). On multivariate analysis, independent risk factors associated with measles death were age <5 years, SC/ST status and non-administration of vitamin A during illness. Outbreaks with longer interval between the occurrence of first case and notification of the outbreak also had a higher rate of deaths.

Conclusions

Measles CFR in Bihar was low. To further reduce case fatality, health authorities need to ensure that SC/ST are targeted by the immunization programme and that outbreak investigations target for vitamin A treatment of cases in high risk groups such as SC/ST and young children and ensure regular visits by health-workers in affected villages to administer vitamin A to new cases.