POLYBROMINATED DIPHENYL ETHERS (PBDES) IN AMERICAN MOTHERS' MILK
No previous reports exist on polybrominated diphenyl ether (PBDE) congeners in individual American mothers' milk. This report on PBDEs is an extension of our previous studies on concentrations of dioxins, dibenzofurans, PCBs, and other chlorinated organics in human milk in a num...
Reflection coefficients of permeant molecules in human red cell suspensions.
Owen, J D; Eyring, E M
1975-08-01
The Staverman reflection coefficient, sigma for several permeant molecules was determined in human red cell suspensions with a Durrum stopped-flow spectrophotometer. This procedure was first used with dog, cat, and beef red cells and with human red cells. The stopped-flow technique used was similar to the rapid-flow method used by those who originally reported sigma measurements in human red cells for molecules which rapidly penetrate the red cell membrane. The sigma values we obtained agreed with those previously reported for most of the slow penetrants, except malonamide, but disagreed with all the sigma values previously reported for the rapid penetrants. We were unable to calculate an "equivalent pore radius" with our sigma data. The advantages of our equipment and our experimental procedure are discussed. Our sigma data suggest that sigma is indirectly proportional to the log of the nonelectrolyte permeability coefficient, omega. Since a similar trend has been previously shown for log omega and molar volume of the permeant molecules, a correlatioo was shown between sigma and molar volume suggesting the membrane acts as a sieve.
Zhang, Helen L.; Mnzava, Kunda W.; Mitchell, Sarah T.; Melubo, Matayo L.; Kibona, Tito J.; Cleaveland, Sarah; Kazwala, Rudovick R.; Crump, John A.; Sharp, Joanne P.; Halliday, Jo E. B.
2016-01-01
Background Zoonoses are common causes of human and livestock illness in Tanzania. Previous studies have shown that brucellosis, leptospirosis, and Q fever account for a large proportion of human febrile illness in northern Tanzania, yet they are infrequently diagnosed. We conducted this study to assess awareness and knowledge regarding selected zoonoses among healthcare providers in Moshi, Tanzania; to determine what diagnostic and treatment protocols are utilized; and obtain insights into contextual factors contributing to the apparent under-diagnosis of zoonoses. Methodology/Results We conducted a questionnaire about zoonoses knowledge, case reporting, and testing with 52 human health practitioners and 10 livestock health providers. Immediately following questionnaire administration, we conducted semi-structured interviews with 60 of these respondents, using the findings of a previous fever etiology study to prompt conversation. Sixty respondents (97%) had heard of brucellosis, 26 (42%) leptospirosis, and 20 (32%) Q fever. Animal sector respondents reported seeing cases of animal brucellosis (4), rabies (4), and anthrax (3) in the previous 12 months. Human sector respondents reported cases of human brucellosis (15, 29%), rabies (9, 18%) and anthrax (6, 12%). None reported leptospirosis or Q fever cases. Nineteen respondents were aware of a local diagnostic test for human brucellosis. Reports of tests for human leptospirosis or Q fever, or for any of the study pathogens in animals, were rare. Many respondents expressed awareness of malaria over-diagnosis and zoonoses under-diagnosis, and many identified low knowledge and testing capacity as reasons for zoonoses under-diagnosis. Conclusions This study revealed differences in knowledge of different zoonoses and low case report frequencies of brucellosis, leptospirosis, and Q fever. There was a lack of known diagnostic services for leptospirosis and Q fever. These findings emphasize a need for improved diagnostic capacity alongside healthcare provider education and improved clinical guidelines for syndrome-based disease management to provoke diagnostic consideration of locally relevant zoonoses in the absence of laboratory confirmation. PMID:26943334
Sing, Andreas; Konrad, Regina; Meinel, Dominik M; Mauder, Norman; Schwabe, Ingo; Sting, Reinhard
2016-08-01
Corynebacterium diphtheriae, the classical causative agent of diphtheria, is considered to be nearly restricted to humans. Here we report the first finding of a non-toxigenic C. diphtheriae biovar belfanti strain in a free-roaming wild animal. The strain obtained from the subcutis and mammary gland of a dead red fox (Vulpes vulpes) was characterized by biochemical and molecular methods including MALDI-TOF and Multi Locus Sequence Typing. Since C. diphtheriae infections of animals, usually with close contact to humans, are reported only very rarely, an intense review comprising also scientific literature from the beginning of the 20th century was performed. Besides the present case, only 11 previously reported C. diphtheriae animal infections could be verified using current scientific criteria. Our report is the first on the isolation of C. diphtheriae from a wildlife animal without any previous human contact. In contrast, the very few unambiguous publications on C. diphtheriae in animals referred to livestock or pet animals with close human contact. C. diphtheriae carriage in animals has to be considered as an exceptionally rare event.
Human fascioliasis with biliary complications.
Kumari, V; Banerjee, Tuhina; Negi, N; Gupta, M I; Tiwari, K; Gupta, M
2013-01-01
We report a case of human fascioliasis adding to the few of the previously reported cases in India. A young boy from rural background in Bihar presented with diarrhea, vomiting, hepatic tenderness, jaundice and fever along with peripheral eosinophilia. Examination of stool revealed yellow-brown eggs of Fasciola hepatica. Human fascioliasis should be kept in mind in patients with cholangitis and eosinophilia especially in areas of sporadic occurrence.
Molecular Diagnosis of Human Taenia martis Eye Infection
Koch, Till; Schoen, Christoph; Muntau, Birgit; Addo, Marylyn; Ostertag, Helmut; Wiechens, Burkhard; Tappe, Dennis
2016-01-01
Taenia martis, a tapeworm harbored in the intestine of mustelids, is a rarely encountered zoonotic cysticercosis pathogen. The larval stage closely resembles the Taenia solium cysticercus, but the natural host and thus the epidemiology of the disease is different. We here report a human eye infection diagnosed molecularly in a previously healthy female German patient. The case represents the third human infection described worldwide; the two previous cases were also European, involving eye and brain. PMID:26928837
MANAGEMENT OF ENDOMETRIOSIS IN TWO CAPTIVE MANDRILLS (MANDRILLUS SPHINX).
Okeson, Danelle M; Higbie, Christine T; Mylniczenko, Natalie D; Haynes, April; Bennett, Suzanne; Klocke, Emily; Carpenter, James W
2016-06-01
Endometriosis has been reported in humans, great apes, and Old World monkeys. Although cases are noted anecdotally in Mandrillus spp., and a previously reported case was noted on postmortem examination, to the authors' knowledge, no previous reports of case management have been published in the peer-reviewed literature. This paper describes the medical and surgical management of endometriosis in two mandrills (Mandrillus sphinx).
Identification and genetic mapping of a homeobox gene to the 4p16. 1 region of human chromosome 4
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stadler, H.S.; Padanilam, B.J.; Solursh, M.
1992-12-01
A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4P16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3[prime] untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of themore » H6 Homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster. 53 refs., 5 figs., 2 tabs.« less
Previous experience in manned space flight: A survey of human factors lessons learned
NASA Technical Reports Server (NTRS)
Chandlee, George O.; Woolford, Barbara
1993-01-01
Previous experience in manned space flight programs can be used to compile a data base of human factors lessons learned for the purpose of developing aids in the future design of inhabited spacecraft. The objectives are to gather information available from relevant sources, to develop a taxonomy of human factors data, and to produce a data base that can be used in the future for those people involved in the design of manned spacecraft operations. A study is currently underway at the Johnson Space Center with the objective of compiling, classifying, and summarizing relevant human factors data bearing on the lessons learned from previous manned space flights. The research reported defines sources of data, methods for collection, and proposes a classification for human factors data that may be a model for other human factors disciplines.
1994-02-14
Observations Gastritis has been reported in cases of ingestion of DF.14 There were no r•po,-ts of effects on humans from wartime usage of DF as an...described. b. Respiratory Effects There are numerous case reports of humans with pulmonary lesions, such as granulomas and pneumonias, following oral or...thcse previously described for the rats. Accidental ingesticn of ZnCI2 by humans has been reported . Severe cases of fcod poisoning have deve!oped in
Mohd Nor, Fadzilah; Tan, Lian Huat; Na, Shi Ling; Ng, Kee Peng
2015-08-01
Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient's cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/µl in two previously published reports, while another report documented CD4 count as 56/µl. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.
Annotated bibliography of human factors applications literature
DOE Office of Scientific and Technical Information (OSTI.GOV)
McCafferty, D.B.
1984-09-30
This bibliography was prepared as part of the Human Factors Technology Project, FY 1984, sponsored by the Office of Nuclear Safety, US Department of Energy. The project was conducted by Lawrence Livermore National Laboratory, with Essex Corporation as a subcontractor. The material presented here is a revision and expansion of the bibliographic material developed in FY 1982 as part of a previous Human Factors Technology Project. The previous bibliography was published September 30, 1982, as Attachment 1 to the FY 1982 Project Status Report.
Molecular Diagnosis of Human Taenia martis Eye Infection.
Koch, Till; Schoen, Christoph; Muntau, Birgit; Addo, Marylyn; Ostertag, Helmut; Wiechens, Burkhard; Tappe, Dennis
2016-05-04
Taenia martis, a tapeworm harbored in the intestine of mustelids, is a rarely encountered zoonotic cysticercosis pathogen. The larval stage closely resembles the Taenia solium cysticercus, but the natural host and thus the epidemiology of the disease is different. We here report a human eye infection diagnosed molecularly in a previously healthy female German patient. The case represents the third human infection described worldwide; the two previous cases were also European, involving eye and brain. © The American Society of Tropical Medicine and Hygiene.
Aghajanirefah, A; Nguyen, L N; Ohadi, M
2016-01-15
Recent emerging evidence indicates that changes in gene expression levels are linked to human evolution. We have previously reported a human-specific nucleotide in the promoter sequence of the calreticulin (CALR) gene at position -220C, which is the site of action of valproic acid. Reversion of this nucleotide to the ancestral A-allele has been detected in patients with degrees of deficit in higher brain cognitive functions. This mutation has since been reported in the 1000 genomes database at an approximate frequency of <0.0004 in humans (rs138452745). In the study reported here, we present update on the status of rs138452745 across evolution, based on the Ensembl and NCBI databases. The DNA pulldown assay was also used to identify the proteins binding to the C- and A-alleles, using two cell lines, SK-N-BE and HeLa. Consistent with our previous findings, the C-allele is human-specific, and the A-allele is the rule across all other species (N=38). This nucleotide resides in a block of 12-nucleotides that is strictly conserved across evolution. The DNA pulldown experiments revealed that in both SK-N-BE and HeLa cells, the transcription repressor BEN domain containing 3 (BEND3) binds to the human-specific C-allele, whereas the nuclear factor I (NFI) family members, NF1A, B, C, and X, specifically bind to the ancestral A-allele. This binding pattern is consistent with a previously reported decreased promoter activity of the C-allele vs. the A-allele. We propose that there is a link between binding of BEND3 to the CALR rs138452745 C-allele and removal of NFI binding site from this nucleotide, and the evolution of human-specific higher brain functions. To our knowledge, CALR rs138452745 is the first instance of enormous nucleotide conservation across evolution, except in the human species. Copyright © 2015 Elsevier B.V. All rights reserved.
Gene organization and alternative splicing of human prohormone convertase PC8.
Goodge, K A; Thomas, R J; Martin, T J; Gillespie, M T
1998-01-01
The mammalian Ca2+-dependent serine protease prohormone convertase PC8 is expressed ubiquitously, being transcribed as 3.5, 4.3 and 6.0 kb mRNA isoforms in various tissues. To determine the origin of these various mRNA isoforms we report the characterization of the human PC8 gene, which has been previously localized to chromosome 11q23-24. Consisting of 16 exons, the human PC8 gene spans approx. 27 kb. A comparison of the position of intron-exon junctions of the human PC8 gene with the gene structures of previously reported prohormone convertase genes demonstrated a divergence of the human PC8 from the highly conserved nature of the gene organization of this enzyme family. The nucleotide sequence of the 5'-flanking region of the human PC8 is reported and possesses putative promoter elements characteristic of a GC-rich promoter. Further supporting the potential role of a GC-rich promoter element, multiple transcriptional initiation sites within a 200 bp region were demonstrated. We propose that the various mRNA isoforms of PC8 result from the inclusion of intronic sequences within transcripts. PMID:9820811
West Nile virus activity--United States, January 1-December 1, 2005.
2005-12-16
West Nile virus (WNV) is the leading cause of arboviral encephalitis in the United States. Originally discovered in Africa in 1937, WNV was first detected in the western hemisphere in 1999 in New York City. Since then it has caused seasonal epidemics of febrile illness and severe neurologic disease. During January 1-December 1, 2005, a total of 2,744 cases of WNV disease in humans were reported in the United States, an increase from 2,359 during the same period in 2004. A total of 1,165 cases were WNV neuroinvasive disease (WNND). WNV infections in humans, birds, mosquitoes, and nonhuman mammals are reported to CDC through ArboNET, an Internet-based arbovirus surveillance system managed by state health departments and CDC. During 2005, WNV transmission to humans or animals expanded into 21 counties that had not previously reported transmission and recurred in 1,196 counties where transmission had been reported in previous years. This report summarizes provisional WNV surveillance data through December 1, 2005, and highlights the need for ongoing surveillance, mosquito control, promotion of personal protection from mosquito bites, and research into additional prevention strategies.
Crossing the Threshold of Rocket Mail: E-Mail Use by U.S. Humanities Faculty.
ERIC Educational Resources Information Center
Bridges, Anne E.; Clement, Russell T.
1997-01-01
Discusses the use of e-mail by humanities faculty based on an e-mail survey of faculty at Brigham Young University (Utah) and the University of Tennessee at Knoxville. Results indicate that humanities faculty are significantly heavier e-mail users than previously reported. (LRW)
The Changing Human Resources Function. Report Number 950.
ERIC Educational Resources Information Center
Freedman, Audrey
The role of the top human resources executive in major corporations has changed during the past decade into a directly involved business advisor, strategist, and implementer of business objectives. Intense competition has overridden previous human resources concerns and forced priorities toward internal, business-driven issues. Since cost-cutting…
ERIC Educational Resources Information Center
Oliveri, María Elena; Tannenbaum, Richard J.
2017-01-01
This report explores the ways in which human resource (HR) managers use "TOEIC"® scores to inform hiring, promotion, and training decisions in an international workplace. Two data sources were used (a) previously collected test users' testimonials that described managers' use of TOEIC scores to inform HR decisions and (b) test-use…
Analysis of Long Bone and Vertebral Failure Patterns
1985-02-14
have disc-shaped epiphyses on the surfaces of the vertebral bodies (Schmorl and Junghanns, 1959). Humans, ]< orangutans , gorillas...The annular epiphysis has been previously reported in humans, orangutans , gorillas, and marmosets (Schmorl and Junghanns, 1959; Bernick, et al
Leucine Rich α-2 Glycoprotein: A Novel Neutrophil Granule Protein and Modulator of Myelopoiesis
Druhan, Lawrence J.; Lance, Amanda; Li, Shimena; Price, Andrea E.; Emerson, Jacob T.; Baxter, Sarah A.; Gerber, Jonathan M.; Avalos, Belinda R.
2017-01-01
Leucine-rich α2 glycoprotein (LRG1), a serum protein produced by hepatocytes, has been implicated in angiogenesis and tumor promotion. Our laboratory previously reported the expression of LRG1 in murine myeloid cell lines undergoing neutrophilic granulocyte differentiation. However, the presence of LRG1 in primary human neutrophils and a role for LRG1 in regulation of hematopoiesis have not been previously described. Here we show that LRG1 is packaged into the granule compartment of human neutrophils and secreted upon neutrophil activation to modulate the microenvironment. Using immunofluorescence microscopy and direct biochemical measurements, we demonstrate that LRG1 is present in the peroxidase-negative granules of human neutrophils. Exocytosis assays indicate that LRG1 is differentially glycosylated in neutrophils, and co-released with the secondary granule protein lactoferrin. Like LRG1 purified from human serum, LRG1 secreted from activated neutrophils also binds cytochrome c. We also show that LRG1 antagonizes the inhibitory effects of TGFβ1 on colony growth of human CD34+ cells and myeloid progenitors. Collectively, these data invoke an additional role for neutrophils in innate immunity that has not previously been reported, and suggest a novel mechanism whereby neutrophils may modulate the microenvironment via extracellular release of LRG1. PMID:28081565
Cryptosporidium ubiquitum n.sp. in animals and humans
USDA-ARS?s Scientific Manuscript database
A new species, Cryptosporidium ubiquitum, previously identified as the Cryptosporidium cervine genotype is described. In published studies the cervine genotype was reported in wild and domesticated ruminants, rodents, carnivores, and primates including humans. Molecular data for C. ubiquitum have b...
Anthropogenic antibiotic resistance genes mobilization to the polar regions.
Hernández, Jorge; González-Acuña, Daniel
2016-01-01
Anthropogenic influences in the southern polar region have been rare, but lately microorganisms associated with humans have reached Antarctica, possibly from military bases, fishing boats, scientific expeditions, and/or ship-borne tourism. Studies of seawater in areas of human intervention and proximal to fresh penguin feces revealed the presence of Escherichia coli strains least resistant to antibiotics in penguins, whereas E. coli from seawater elsewhere showed resistance to one or more of the following antibiotics: ampicillin, tetracycline, streptomycin, and trim-sulfa. In seawater samples, bacteria were found carrying extended-spectrum β-lactamase (ESBL)-type CTX-M genes in which multilocus sequencing typing (MLST) showed different sequence types (STs), previously reported in humans. In the Arctic, on the contrary, people have been present for a long time, and the presence of antibiotic resistance genes (ARGs) appears to be much more wide-spread than was previously reported. Studies of E coli from Arctic birds (Bering Strait) revealed reduced susceptibility to antibiotics, but one globally spreading clone of E. coli genotype O25b-ST131, carrying genes of ESBL-type CTX-M, was identified. In the few years between sample collections in the same area, differences in resistance pattern were observed, with E. coli from birds showing resistance to a maximum of five different antibiotics. Presence of resistance-type ESBLs (TEM, SHV, and CTX-M) in E. coli and Klebsiella pneumoniae was also confirmed by specified PCR methods. MLST revealed that those bacteria carried STs that connect them to previously described strains in humans. In conclusion, bacteria previously related to humans could be found in relatively pristine environments, and presently human-associated, antibiotic-resistant bacteria have reached a high global level of distribution that they are now found even in the polar regions.
Finding the CO[subscript 2] Culprit
ERIC Educational Resources Information Center
Clary, Renee; Wandersee, James
2015-01-01
In 2013, the Intergovernmental Panel on Climate Change (IPCC) released its fifth report, attributing 95% of "all" climate warming--from the 1950s through today--to humans. Not only did the report--like previous IPCC reports dating back to 1990--accredit global warming to anthropogenic carbon dioxide emissions, but over time the vast…
Anterior temporal face patches: a meta-analysis and empirical study
Von Der Heide, Rebecca J.; Skipper, Laura M.; Olson, Ingrid R.
2013-01-01
Evidence suggests the anterior temporal lobe (ATL) plays an important role in person identification and memory. In humans, neuroimaging studies of person memory report consistent activations in the ATL to famous and personally familiar faces and studies of patients report resection or damage of the ATL causes an associative prosopagnosia in which face perception is intact but face memory is compromised. In addition, high-resolution fMRI studies of non-human primates and electrophysiological studies of humans also suggest regions of the ventral ATL are sensitive to novel faces. The current study extends previous findings by investigating whether similar subregions in the dorsal, ventral, lateral, or polar aspects of the ATL are sensitive to personally familiar, famous, and novel faces. We present the results of two studies of person memory: a meta-analysis of existing fMRI studies and an empirical fMRI study using optimized imaging parameters. Both studies showed left-lateralized ATL activations to familiar individuals while novel faces activated the right ATL. Activations to famous faces were quite ventral, similar to what has been reported in previous high-resolution fMRI studies of non-human primates. These findings suggest that face memory-sensitive patches in the human ATL are in the ventral/polar ATL. PMID:23378834
Niki, Chiharu; Maruyama, Takashi; Muragaki, Yoshihiro; Kumada, Takatsune
2014-01-01
Background. Perseveration has been observed in a number of behavioural contexts, including speaking, writing, and drawing. However, no previous report describes patients who show perseveration only for drawing a human figure. Objective. The present report describes a group of patients who show body awareness-related cognitive impairment during a human figure drawing task, a different presentation from previously described neuropsychological cases. Methods. Participants were 15 patients who had a frontal lobe brain tumour around the insula cortex of the right hemisphere and had subsequently undergone a neurosurgical resective operation. Participants were asked to draw a human figure in both “hands-down” and “hands-up” configurations. Results. Eight of the 15 patients drew a human figure with six fingers during the “hands-up” and the “hands-down” human figure drawing tasks (one patient drew eight fingers). A statistical analysis of potential lesion areas revealed damage to the right anterior frontal insula and operculum in this group of patients relative to the five-finger drawing group. Conclusions. Our findings reveal a newly described neuropsychological phenomenon that could reflect impairment in attention directed towards body representations. PMID:24876665
Whole-Genome Characterization of a Novel Human Influenza A(H1N2) Virus Variant, Brazil
Born, Priscila Silva; Matos, Aline Rocha; Motta, Fernando Couto; Caetano, Braulia Costa; Debur, Maria do Carmo; Riediger, Irina Nastassja; Brown, David; Siqueira, Marilda M.
2017-01-01
We report the characterization of a novel reassortant influenza A(H1N2) virus not previously reported in humans. Recovered from a a pig farm worker in southeast Brazil who had influenza-like illness, this virus is a triple reassortant containing gene segments from subtypes H1N2 (hemagglutinin), H3N2 (neuraminidase), and pandemic H1N1 (remaining genes). PMID:27983507
Whole-Genome Characterization of a Novel Human Influenza A(H1N2) Virus Variant, Brazil.
Resende, Paola Cristina; Born, Priscila Silva; Matos, Aline Rocha; Motta, Fernando Couto; Caetano, Braulia Costa; Debur, Maria do Carmo; Riediger, Irina Nastassja; Brown, David; Siqueira, Marilda M
2017-01-01
We report the characterization of a novel reassortant influenza A(H1N2) virus not previously reported in humans. Recovered from a a pig farm worker in southeast Brazil who had influenza-like illness, this virus is a triple reassortant containing gene segments from subtypes H1N2 (hemagglutinin), H3N2 (neuraminidase), and pandemic H1N1 (remaining genes).
The Incidence of Human Papillomavirus in Tanzanian Adolescent Girls Before Reported Sexual Debut.
Houlihan, Catherine F; Baisley, Kathy; Bravo, Ignacio G; Kapiga, Saidi; de Sanjosé, Silvia; Changalucha, John; Ross, David A; Hayes, Richard J; Watson-Jones, Deborah
2016-03-01
Acquisition of human papillomavirus (HPV) in women occurs predominantly through vaginal sex. However, HPV has been detected in girls reporting no previous sex. We aimed to determine incidence and risk factors for HPV acquisition in girls who report no previous sex in Tanzania, a country with high HPV prevalence and cervical cancer incidence. We followed 503 adolescent girls aged 15-16 years in Mwanza, Tanzania, with face-to-face interviews and self-administered vaginal swabs every 3 months for 18 months; 397 girls reported no sex before enrollment or during follow-up; of whom, 120 were randomly selected. Samples from enrollment, 6-, 12-, and 18-month visits were tested for 37 HPV genotypes. Incidence, clearance, point prevalence, and duration of any HPV and genotype-specific infections were calculated and associated factors were evaluated. Of 120 girls who reported no previous sex, 119 were included, contributing 438 samples. HPV was detected in 51 (11.6%) samples. The overall incidence of new HPV infections was 29.4/100 person-years (95% confidence interval: 15.9-54.2). The point prevalence of vaccine types HPV-6,-11,-16, and -18 was .9%, .9%, 2.0%, and 0%, respectively. Spending a night away from home and using the Internet were associated with incident HPV, and reporting having seen a pornographic movie was inversely associated with HPV incidence. Incident HPV infections were detected frequently in adolescent girls who reported no previous sex over 18 months. This is likely to reflect under-reporting of sex. A low-point prevalence of HPV genotypes in licensed vaccines was seen, indicating that vaccination of these girls might still be effective. Copyright © 2016 Society for Adolescent Health and Medicine. All rights reserved.
The Incidence of Human Papillomavirus in Tanzanian Adolescent Girls Before Reported Sexual Debut
Houlihan, Catherine F.; Baisley, Kathy; Bravo, Ignacio G.; Kapiga, Saidi; de Sanjosé, Silvia; Changalucha, John; Ross, David A.; Hayes, Richard J.; Watson-Jones, Deborah
2016-01-01
Purpose Acquisition of human papillomavirus (HPV) in women occurs predominantly through vaginal sex. However, HPV has been detected in girls reporting no previous sex. We aimed to determine incidence and risk factors for HPV acquisition in girls who report no previous sex in Tanzania, a country with high HPV prevalence and cervical cancer incidence. Methods We followed 503 adolescent girls aged 15–16 years in Mwanza, Tanzania, with face-to-face interviews and self-administered vaginal swabs every 3 months for 18 months; 397 girls reported no sex before enrollment or during follow-up; of whom, 120 were randomly selected. Samples from enrollment, 6-, 12-, and 18-month visits were tested for 37 HPV genotypes. Incidence, clearance, point prevalence, and duration of any HPV and genotype-specific infections were calculated and associated factors were evaluated. Results Of 120 girls who reported no previous sex, 119 were included, contributing 438 samples. HPV was detected in 51 (11.6%) samples. The overall incidence of new HPV infections was 29.4/100 person-years (95% confidence interval: 15.9–54.2). The point prevalence of vaccine types HPV-6,-11,-16, and -18 was .9%, .9%, 2.0%, and 0%, respectively. Spending a night away from home and using the Internet were associated with incident HPV, and reporting having seen a pornographic movie was inversely associated with HPV incidence. Conclusions Incident HPV infections were detected frequently in adolescent girls who reported no previous sex over 18 months. This is likely to reflect under-reporting of sex. A low-point prevalence of HPV genotypes in licensed vaccines was seen, indicating that vaccination of these girls might still be effective. PMID:26725717
Detection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage▿ †
Loh, Joy; Zhao, Guoyan; Presti, Rachel M.; Holtz, Lori R.; Finkbeiner, Stacy R.; Droit, Lindsay; Villasana, Zoilmar; Todd, Collin; Pipas, James M.; Calgua, Byron; Girones, Rosina; Wang, David; Virgin, Herbert W.
2009-01-01
The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the asfarvirus family but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among asfarviruses than previously thought and raises the possibility that human infection by asfarviruses may occur. PMID:19812170
40 CFR 80.1451 - What are the reporting requirements under the RFS program?
Code of Federal Regulations, 2014 CFR
2014-07-01
... interior spaces of homes or buildings to control ambient climate for human comfort, and for no other... explanation of any change in land use from the previous year. (4) On an annual basis, the report from an...
Arsenic exposure via contaminated drinking water is a great public health concern worldwide. Chronic arsenic exposure has been associated with human skin, lung and bladder cancer and other chronic effects. We have previous reported that sodium arsenite stimulated cell proliferati...
Animate and Inanimate Objects in Human Visual Cortex: Evidence for Task-Independent Category Effects
ERIC Educational Resources Information Center
Wiggett, Alison J.; Pritchard, Iwan C.; Downing, Paul E.
2009-01-01
Evidence from neuropsychology suggests that the distinction between animate and inanimate kinds is fundamental to human cognition. Previous neuroimaging studies have reported that viewing animate objects activates ventrolateral visual brain regions, whereas inanimate objects activate ventromedial regions. However, these studies have typically…
USDA-ARS?s Scientific Manuscript database
Worldwide, reports document the increasing frequency of methicillin resistant Staphylococcus aureus (MRSA) infections. Other human pathogens are recognized as unresponsive to antibiotics of last resort. These previously treatable infections now account for increased numbers of human disease and de...
Plague in Iran: its history and current status.
Hashemi Shahraki, Abdolrazagh; Carniel, Elizabeth; Mostafavi, Ehsan
2016-01-01
Plague remains a public health concern worldwide, particularly in old foci. Multiple epidemics of this disease have been recorded throughout the history of Iran. Despite the long-standing history of human plague in Iran, it remains difficult to obtain an accurate overview of the history and current status of plague in Iran. In this review, available data and reports on cases and outbreaks of human plague in the past and present in Iran and in neighboring countries were collected, and information was compiled regarding when, where, and how many cases occurred. This paper considers the history of plague in Persia (the predecessor of today's Iran) and has a brief review of plague in countries in the World Health Organization Eastern Mediterranean Region, including a range of countries in the Middle East and North Africa. Since Iran has experienced outbreaks of plague for several centuries, neighboring countries have reported the disease in recent years, the disease can be silent for decades, and the circulation of Yersinia pestis has been reported among rodents and dogs in western Iran, more attention should be paid to disease monitoring in areas with previously reported human cases and in high-risk regions with previous epizootic and enzootic activity.
Femoral Prosthesis Infection by Rhodotorula mucilaginosa▿
Savini, Vincenzo; Sozio, Federica; Catavitello, Chiara; Talia, Marzia; Manna, Assunta; Febbo, Fabio; Balbinot, Andrea; Di Bonaventura, Giovanni; Piccolomini, Raffaele; Parruti, Giustino; D'Antonio, Domenico
2008-01-01
This case report is a case history of a femoral prosthesis infection caused by Rhodotorula mucilaginosa in a human immunodeficiency virus patient. Though the pathogenicity of this organism for bone tissue has been previously reported, this is the first reported case of an orthopedic prosthesis infection by this species of the genus Rhodotorula. PMID:18753353
Complex torso reconstruction with human acellular dermal matrix: long-term clinical follow-up.
Nemeth, Nicole L; Butler, Charles E
2009-01-01
Although reports have demonstrated good early outcomes with human acellular dermal matrix even when used for complex, contaminated defects, no long-term outcomes have been reported. The authors reviewed the long-term outcomes of 13 patients who had complex torso reconstructions that included human acellular dermal matrix. All patients were at increased risk for mesh-related complications. Eight patients died as a result of progression of their oncologic disease at a mean of 258 days postoperatively. The mean follow-up for the remaining five patients was 43.7 months. Six patients had early complications (none were human acellular dermal matrix-related) and were reported on previously. Two patients had developed complications since the initial report. One patient developed a flap donor-site seroma remote from the reconstruction site, and another developed a recurrent ventral hernia. No patients have required additional surgery for human acellular dermal matrix-related complications. This follow-up report indicates that human acellular dermal matrix repair of large, complex torso defects can result in good long-term outcomes even when patients are at high risk for mesh-related complications.
Severe human Babesia divergens infection in Norway.
Mørch, K; Holmaas, G; Frolander, P S; Kristoffersen, E K
2015-04-01
Human babesiosis is a rare but potentially life-threatening parasitic disease transmitted by ixodid ticks, and has not previously been reported in Norway. We report a case of severe babesiosis that occurred in Norway in 2007. The patient had previously undergone a splenectomy. He was frequently exposed to tick bites in an area endemic for bovine babesiosis in the west of Norway. The patient presented with severe haemolysis and multiorgan failure. Giemsa-stained blood smears revealed 30% parasitaemia with Babesia spp. He was treated with quinine in combination with clindamycin, apheresis, and supportive treatment with ventilatory support and haemofiltration, and made a complete recovery. This is the first case reported in Norway; however Babesia divergens seroprevalence in cattle in Norway is high, as is the risk of Ixodes ricinus tick bite in the general population. Babesiosis should be considered in the differential diagnosis of unexplained febrile haemolytic disease. Copyright © 2015. Published by Elsevier Ltd.
Supsrisunjai, Chavalit; Kootiratrakarn, Tanawatt; Puangpet, Pailin; Bunnag, Thareena; Chaowalit, Prapaipit; Wessagowit, Vesarat
2017-05-01
AbstractSeveral case reports of autochthonous leishmaniasis in Thailand have been published since 1996. Most of the previous cases presented with visceral leishmaniasis (VL) and were mostly reported in southern part of Thailand. Recently, it has been evident that Leishmania martiniquensis is the main cause of Leishmania infection in Thailand. However, Leishmania siamensis (PCM2 Trang isolate) was found to be of a separate lineage with restricted distribution in southern Thailand and also a cause of disseminated dermal and visceral leishmaniasis in one published case. Here we report the first patient from central Thailand with human immunodeficiency virus infection presenting with disseminated dermal leishmaniasis. Polymerase chain reaction and DNA sequencing analysis (large subunit of RNA polymerase II and 18S ribosomal RNA internal transcribed spacer 1) from the tissue biopsy sample revealed the pathogen sequences to be highly homologous to PCM2 Trang strain previously reported from southern Thailand.
Supsrisunjai, Chavalit; Kootiratrakarn, Tanawatt; Puangpet, Pailin; Bunnag, Thareena; Chaowalit, Prapaipit; Wessagowit, Vesarat
2017-01-01
Several case reports of autochthonous leishmaniasis in Thailand have been published since 1996. Most of the previous cases presented with visceral leishmaniasis (VL) and were mostly reported in southern part of Thailand. Recently, it has been evident that Leishmania martiniquensis is the main cause of Leishmania infection in Thailand. However, Leishmania siamensis (PCM2 Trang isolate) was found to be of a separate lineage with restricted distribution in southern Thailand and also a cause of disseminated dermal and visceral leishmaniasis in one published case. Here we report the first patient from central Thailand with human immunodeficiency virus infection presenting with disseminated dermal leishmaniasis. Polymerase chain reaction and DNA sequencing analysis (large subunit of RNA polymerase II and 18S ribosomal RNA internal transcribed spacer 1) from the tissue biopsy sample revealed the pathogen sequences to be highly homologous to PCM2 Trang strain previously reported from southern Thailand. PMID:28138050
Galli, Uwe M; Sauter, Marlies; Lecher, Bernd; Maurer, Simone; Herbst, Hermann; Roemer, Klaus; Mueller-Lantzsch, Nikolaus
2005-04-28
Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs. We report here that mice that inducibly express HERV-K rec show a disturbed germ cell development and may exhibit, by 19 months of age, changes reminiscent of carcinoma in situ, the predecessor lesion of classic seminoma in humans. This provides the first direct evidence that the expression of a human endogenous retroviral gene previously established as a marker in human germ cell tumors may contribute to organ-specific tumorigenesis in a transgenic mouse model.
Ozkul, Aykut; Ergunay, Koray; Koysuren, Aydan; Alkan, Feray; Arsava, Ethem M; Tezcan, Seda; Emekdas, Gurol; Hacioglu, Sabri; Turan, Mahur; Us, Durdal
2013-07-01
West Nile fever is an important zoonotic infection caused by West Nile virus (WNV), a member of the Flaviviridae. Previous serological data from Turkey suggest widespread WNV circulation. This report includes cases of human and equine WNV infections occurring concurrently, and manifesting as central nervous system infections, in two neighboring provinces of Central Anatolia, Turkey. A partial phylogenetic analysis of the causative virus is given for the first time. The cases were reported in February (horses) and March (human). Symptoms of the disease were similar in the two species, characterized by neurological manifestations suggesting meningoencephalitis. Real-time/nested PCRs and commercial immunoassays and a plaque reduction neutralization assay were employed for the detection of viral RNA and specific antibodies, respectively. WNV RNAs were detected in buffy coat (horses) and cerebrospinal fluid (human) samples. Partial nucleotide sequences of the E-gene coding region revealed that the strains are closely related to viruses of lineage 1, clade 1a. Accompanying equine serosurveillance demonstrated WNV-specific antibodies in 31.6% of the samples. This is the first report of acute WNV infections caused by lineage 1 strains from Turkey, in concordance with previous reports from some European and North African countries. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Possible Transmission of Irkut Virus from Dogs to Humans.
Chen, Teng; Miao, Fa Ming; Liu, Ye; Zhang, Shou Feng; Zhang, Fei; Li, Nan; Hu, Rong Liang
2018-02-01
Lyssaviruses, including Rabies virus, Duvenhage virus, European bat lyssavirus 1, European bat lyssavirus 2, Australian bat lyssavirus, and Irkut virus (IRKV), have caused human fatalities, but infection of IRKV in dogs has not been previously reported. In China, a dead dog that previously bit a human was determined to be infected with IRKV. Pathogenicity tests revealed that IRKVs can cause rabies-like disease in dogs and cats after laboratory infection. The close relationship between humans and pets, such as dogs and cats, may generate a new spillover-spreading route for IRKV infection. Therefore, additional attention should be paid to trans-species infection of IRKV between bats and dogs or dogs and humans through investigation of the prevalence and circulation patterns of IRKV in China. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
Observations on the intestinal protozoa infecting man in Rhodesia.
Goldsmid, J M; Rogers, S; Mahomed, K
1976-09-18
Humans in Rhodesia harbour a wide range of intestinal protozoa. Of the species included, Entamoeba histolytica, Entamoeba coli and Giardia lamblia have previously been recorded. Other species which are either rarely reported or which have previously never been reported from this country, include Trichomonas hominis, Chilomastix mesnili, Enteromonas hominis, Retortamonas intestinalis, Balantidum coli,Entamoeba hartmanni,Entamoeba histolytica Laredo. Endolimax nana, Dientamoeba fragilis and Isospora belli. The importance in Rhodesia of these species, and especially of E. histolytica, is discussed.
Kärrman, Anna; Domingo, José L; Llebaria, Xavier; Nadal, Martí; Bigas, Esther; van Bavel, Bert; Lindström, Gunilla
2010-03-01
Perfluorinated compounds (PFCs) are global environmental pollutants that bioaccumulate in wildlife and humans. Laboratory experiments have revealed toxic effects such as delayed development, humoral suppression, and hepatotoxicity. Although numerous human blood levels have been reported, little is known about distribution in the human body. Knowledge about PFC distribution and accumulation in the human body is crucial to understanding uptake and subsequent effects as well as to conduct risk assessments. The present study reports PFC levels in human liver and breast milk from a general population living in Catalonia, Spain. Liver and milk levels are compared to previously reported levels in blood from the same geographic area as well as to other existing reports on human liver and milk levels in other countries. Human liver (n = 12) and milk (n = 10) samples were collected in 2007 and 2008 in Catalonia, Spain. Liver samples were taken postmortem from six males and six females aged 27-79 years. Milk samples were from healthy primipara women (30-39 years old). Both liver and milk were analyzed by solid-phase extraction and ultra-performance liquid chromatography tandem mass spectrometry. Six PFCs were detected in liver, with perfluorooctanesulfonate (PFOS, 26.6 ng/g wet weight) being the chemical with the highest mean concentration. Other PFCs such as perfluorohexanesulfonate (PFHxS), perfluorooctanoic acid (PFOA), and acids with chain lengths up to C11 were also detected, with mean levels ranging between 0.50 and 1.45 ng/g wet weight. On the other hand, PFOS and PFHxS were the only PFCs detected in human milk, with mean concentrations of 0.12 and 0.04 ng/mL, respectively. While milk concentrations were similar to reported levels from other countries, liver samples contained more PFCs above quantification limits and higher PFOS concentrations compared to the only two other reports found in the literature. Differences between the results of the present study and those concerning previous investigations can be due to declining levels of some PFCs, which have been reported for the USA. The relationship between PFC concentrations in human liver, milk, and blood was assessed using blood concentrations previously determined in Catalonia. Those levels resulted in liver/serum ratios of 1.7:1, 1.4:1, and 2.1:1 for PFOS, perfluorodecanoic acid, and perfluoroundecanoic acid, respectively. Accumulation in liver is suggested for PFOS and the perfluorocarboxylic acids with carbon chain lengths C9, C10, and C11. For PFOA and PFHxS, fivefold and 14-fold higher concentrations, respectively, were seen in serum as compared to liver. The mean concentration of PFOS and PFHxS in milk was only 0.8% and 0.6% of the reported mean serum level, respectively. The results of the present study show that several PFCs could be detected in human liver samples of subjects living in Tarragona. Concerning human milk, the mechanism by which PFCs are transferred from mother's blood to breast milk is still unclear. Considering that PFCs are strongly bound to the protein fraction in blood, the possibility of PFCs entering the milk and accumulating to levels observed in maternal plasma is limited. Interestingly, the potential accumulation difference for PFCs with different chain lengths might be of great importance for risk assessment. Continuing studies on the distribution of different PFCs in human tissue are therefore justified.
No Evidence for Impaired Perception of Biological Motion in Adults with Autistic Spectrum Disorders
ERIC Educational Resources Information Center
Murphy, Patrick; Brady, Nuala; Fitzgerald, Michael; Troje, Nikolaus F.
2009-01-01
A central feature of autistic spectrum disorders (ASDs) is a difficulty in identifying and reading human expressions, including those present in the moving human form. One previous study, by Blake et al. (2003), reports decreased sensitivity for perceiving biological motion in children with autism, suggesting that perceptual anomalies underlie…
Intersensory Perception at Birth: Newborns Match Nonhuman Primate Faces and Voices
ERIC Educational Resources Information Center
Lewkowicz, David J.; Leo, Irene; Simion, Francesca
2010-01-01
Previous studies have shown that infants, including newborns, can match previously unseen and unheard human faces and vocalizations. More recently, it has been reported that infants as young as 4 months of age also can match the faces and vocalizations of other species raising the possibility that such broad multisensory perceptual tuning is…
1988-10-28
FIELD GROUP SUBAGROUP Synthetic peptides, anti-idiotypes, vaccines, 06 03 human immunodeficiency virus, chimpanzees, RAI, Virology, 06 13 HTLV III...suppressive effects have been reported previously with a synthetic peptide analogous to amino acid sequences from the feline leukemia virus...on the use of synthetic peptides in human immunodeficiency virus infection. In Advances in Biotechnological Processes (A. Mizrahi, ed.), Alan R. Liss
Trypanosoma lewisi or T. lewisi-like infection in a 37-day-old Indian infant.
Verma, Archana; Manchanda, Samiksha; Kumar, Nirmal; Sharma, Archna; Goel, Masha; Banerjee, Partha Sarathi; Garg, Rajat; Singh, Brahma Pal; Balharbi, Fatima; Lejon, Veerle; Deborggraeve, Stijn; Singh Rana, Udai Veer; Puliyel, Jacob
2011-08-01
Trypanosomes were observed in the peripheral blood smear of a 37-day-old Indian infant admitted off feeds, with fever and convulsions. Trypanosoma (Herpetosoma) lewisi was identified in the blood. The species identification was confirmed by morphometry, polymerase chain reaction, and sequencing. Human infection with this organism is rare. Only seven cases of this infection have been reported previously in humans. The cases reported are reviewed to develop a composite picture of this disease.
Trypanosoma lewisi or T. lewisi-like Infection in a 37-Day-Old Indian Infant
Verma, Archana; Manchanda, Samiksha; Kumar, Nirmal; Sharma, Archna; Goel, Masha; Banerjee, Partha Sarathi; Garg, Rajat; Singh, Brahma Pal; Balharbi, Fatima; Lejon, Veerle; Deborggraeve, Stijn; Singh Rana, Udai Veer; Puliyel, Jacob
2011-01-01
Trypanosomes were observed in the peripheral blood smear of a 37-day-old Indian infant admitted off feeds, with fever and convulsions. Trypanosoma (Herpetosoma) lewisi was identified in the blood. The species identification was confirmed by morphometry, polymerase chain reaction, and sequencing. Human infection with this organism is rare. Only seven cases of this infection have been reported previously in humans. The cases reported are reviewed to develop a composite picture of this disease. PMID:21813838
Endemic pemphigus foliaceus in Venezuela: report of two children.
González, Francisco; Sáenz, Ana Maria; Cirocco, Antonietta; Tacaronte, Inés Maria; Fajardo, Javier Enrique; Calebotta, Adriana
2006-01-01
Two native Yanomami children from the Venezuelan Amazonia with erythroderma were hospitalized on our service. Clinical, histologic, and immunofluorescence studies diagnosed endemic pemphigus foliaceous. Human leukocyte antigen class II showed DRB1*04 subtype *0411, which has not been previously associated with this disease. However, it shares a common epitope with all the human leukocyte antigen DRB1 alleles that have been involved in this disease among Brazilian populations. Although this condition is endemic in Brazil, our patients are the first two reported in Venezuela.
A third genotype of the human parvovirus PARV4 in sub-Saharan Africa.
Simmonds, Peter; Douglas, Jill; Bestetti, Giovanna; Longhi, Erika; Antinori, Spinello; Parravicini, Carlo; Corbellino, Mario
2008-09-01
PARV4 is a recently discovered human parvovirus widely distributed in injecting drug users in the USA and Europe, particularly in those co-infected with human immunodeficiency virus (HIV). Like parvovirus B19, PARV4 persists in previously exposed individuals. In bone marrow and lymphoid tissue, PARV4 sequences were detected in two sub-Saharan African study subjects with AIDS but without a reported history of parenteral exposure and who were uninfected with hepatitis C virus. PARV4 variants infecting these subjects were phylogenetically distinct from genotypes 1 and 2 (formerly PARV5) that were reported previously. Analysis of near-complete genome sequences demonstrated that they should be classified as a third (equidistant) PARV4 genotype. The availability of a further near-complete genome sequence of this novel genotype facilitated identification of conserved novel open reading frames embedded in the ORF2 coding sequence; one encoded a putative protein with identifiable homology to SAT proteins of members of the genus Parvovirus.
Plague in Iran: its history and current status
2016-01-01
OBJECTIVES: Plague remains a public health concern worldwide, particularly in old foci. Multiple epidemics of this disease have been recorded throughout the history of Iran. Despite the long-standing history of human plague in Iran, it remains difficult to obtain an accurate overview of the history and current status of plague in Iran. METHODS: In this review, available data and reports on cases and outbreaks of human plague in the past and present in Iran and in neighboring countries were collected, and information was compiled regarding when, where, and how many cases occurred. RESULTS: This paper considers the history of plague in Persia (the predecessor of today’s Iran) and has a brief review of plague in countries in the World Health Organization Eastern Mediterranean Region, including a range of countries in the Middle East and North Africa. CONCLUSIONS: Since Iran has experienced outbreaks of plague for several centuries, neighboring countries have reported the disease in recent years, the disease can be silent for decades, and the circulation of Yersinia pestis has been reported among rodents and dogs in western Iran, more attention should be paid to disease monitoring in areas with previously reported human cases and in high-risk regions with previous epizootic and enzootic activity. PMID:27457063
Figgatt, Mary; Hyde, James; Dziewulski, David; Wiegert, Eric; Kishbaugh, Scott; Zelin, Grant; Wilson, Lloyd
2017-11-03
Cyanobacteria, also known as blue-green algae, are photosynthetic, aquatic organisms found in fresh, brackish, and marine water around the world (1). Rapid proliferation and accumulation of potentially toxin-producing cyanobacteria characterize one type of harmful algal bloom (HAB). HABs have the potential to cause illness in humans and animals (2,3); however, the epidemiology of these illnesses has not been well characterized. Statewide in 2015, a total of 139 HABs were identified in New York, 97 (70%) of which were confirmed through laboratory analysis; 77 independent beach closures were ordered at 37 beaches on 20 different bodies of water. To better characterize HAB-associated illnesses, during June-September 2015, the New York State Department of Health (NYSDOH) implemented a pilot surveillance system in 16 New York counties. Activities included the collection of data from environmental HAB reports, illness reports, poison control centers, and syndromic surveillance, and increased outreach to the public, health care providers, and veterinarians. During June-September, 51 HAB-associated illnesses were reported, including 35 that met the CDC case definitions*; 32 of the cases occurred in humans and three in dogs. In previous years, New York never had more than 10 HAB-associated illnesses reported statewide. The pilot surveillance results from 16 counties during a 4-month period suggest that HAB-associated illnesses might be more common than previously reported.
Brain activation during human male ejaculation revisited.
Georgiadis, Janniko R; Reinders, A A T Simone; Van der Graaf, Ferdinand H C E; Paans, Anne M J; Kortekaas, Rudie
2007-04-16
In a prior [O]-H2O positron emission tomographic study we reported brain regions involved in human male ejaculation. Here, we used another, more recently acquired data set to evaluate the methodological approach of this previous study, and discovered that part of the reported activation pattern was not related to ejaculation. With a new analysis of these ejaculation data, we now demonstrate ejaculation-related activations in the deep cerebellar nuclei (dentate nucleus), anterior vermis, pons, and ventrolateral thalamus, and, most importantly, ejaculation-related deactivations throughout the prefrontal cortex. This revision offers a new and more accurate insight into the brain regions involved in human male ejaculation.
McCarron, David A; Kazaks, Alexandra G; Geerling, Joel C; Stern, Judith S; Graudal, Niels A
2013-10-01
The recommendation to restrict dietary sodium for management of hypertensive cardiovascular disease assumes that sodium intake exceeds physiologic need, that it can be significantly reduced, and that the reduction can be maintained over time. In contrast, neuroscientists have identified neural circuits in vertebrate animals that regulate sodium appetite within a narrow physiologic range. This study further validates our previous report that sodium intake, consistent with the neuroscience, tracks within a narrow range, consistent over time and across cultures. Peer-reviewed publications reporting 24-hour urinary sodium excretion (UNaV) in a defined population that were not included in our 2009 publication were identified from the medical literature. These datasets were combined with those in our previous report of worldwide dietary sodium consumption. The new data included 129 surveys, representing 50,060 participants. The mean value and range of 24-hour UNaV in each of these datasets were within 1 SD of our previous estimate. The combined mean and normal range of sodium intake of the 129 datasets were nearly identical to that we previously reported (mean = 158.3±22.5 vs. 162.4±22.4 mmol/d). Merging the previous and new datasets (n = 190) yielded sodium consumption of 159.4±22.3 mmol/d (range = 114-210 mmol/d; 2,622-4,830mg/d). Human sodium intake, as defined by 24-hour UNaV, is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries. As documented here, this range is determined by physiologic needs rather than environmental factors. Future guidelines should be based on this biologically determined range.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Abkowitz, M.D.; Abkowitz, S.B.; Lepofsky, M.
1989-04-01
This report examines the extent of human factors effects on the safety of transporting radioactive waste materials. It is seen principally as a scoping effort, to establish whether there is a need for DOE to undertake a more formal approach to studying human factors in radioactive waste transport, and if so, logical directions for that program to follow. Human factors effects are evaluated on driving and loading/transfer operations only. Particular emphasis is placed on the driving function, examining the relationship between human error and safety as it relates to the impairment of driver performance. Although multi-modal in focus, the widespreadmore » availability of data and previous literature on truck operations resulted in a primary study focus on the trucking mode from the standpoint of policy development. In addition to the analysis of human factors accident statistics, the report provides relevant background material on several policies that have been instituted or are under consideration, directed at improving human reliability in the transport sector. On the basis of reported findings, preliminary policy areas are identified. 71 refs., 26 figs., 5 tabs.« less
DOT National Transportation Integrated Search
2001-01-01
This report is part of a continuing effort to develop human factors measures for different operational environments in the Federal Aviation Administration Air Traffic Control (ATC) system. Previous research at the William J. Hughes Technical Center R...
Nalawade-Chavan, Shweta; McCullagh, James; Hedges, Robert
2014-01-01
Sungir (Russia) is a key Mid-Upper Palaeolithic site in Eurasia, containing several spectacular burials that disclose early evidence for complex burial rites in the form of a range of grave goods deposited along with the dead. Dating has been particularly challenging, with multiple radiocarbon dates ranging from 19,160±270 to 28,800±240 BP for burials that are believed to be closely similar in age. There are disparities in the radiocarbon dates of human bones, faunal remains and charcoal found on the floor of burials [1], [2], [3]. Our approach has been to develop compound-specific methods using High Performance Liquid Chromatography (HPLC) to separate single amino acids, such as hydroxyproline, and thereby avoid the known human contamination on the bones themselves. Previously, we applied this technique to obtain radiocarbon dates of ∼30,000 BP for Sungir 2, Sungir 3 and a mammoth bone from the occupation levels of the site [4]. The single amino acid radiocarbon dates were in good agreement with each other compared to all the dates previously reported, supporting their reliability. Here we report new hydroxyproline dates for two more human burials from the same site, Sungir 1 and Sungir 4. All five hydroxyproline dates reported are statistically indistinguishable and support an identical age for the group. The results suggest that compound-specific radiocarbon analysis should be considered seriously as the method of choice when precious archaeological remains are to be dated because they give a demonstrably contaminant-free radiocarbon age. The new ages are, together with the previously dated ‘Red Lady of Paviland’ human in the British Isles, the earliest for Mid Upper Palaeolithic burial behaviour in Eurasia, and point to the precocious appearance of this form of rite in Europe Russia. PMID:24416120
Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.
Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan
2014-02-01
Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.
A New Small-Molecule Antagonist Inhibits Graves' Disease Antibody Activation of the TSH Receptor
Eliseeva, Elena; McCoy, Joshua G.; Napolitano, Giorgio; Giuliani, Cesidio; Monaco, Fabrizio; Huang, Wenwei; Gershengorn, Marvin C.
2011-01-01
Context: Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate the TSH receptor (TSHR). We previously reported the first small-molecule antagonist of human TSHR and showed that it inhibited receptor signaling stimulated by sera from four patients with GD. Objective: Our objective was to develop a better TSHR antagonist and use it to determine whether inhibition of TSAb activation of TSHR is a general phenomenon. Design: We aimed to chemically modify a previously reported small-molecule TSHR ligand to develop a better antagonist and determine whether it inhibits TSHR signaling by 30 GD sera. TSHR signaling was measured in two in vitro systems: model HEK-EM293 cells stably overexpressing human TSHRs and primary cultures of human thyrocytes. TSHR signaling was measured as cAMP production and by effects on thyroid peroxidase mRNA. Results: We tested analogs of a previously reported small-molecule TSHR inverse agonist and selected the best NCGC00229600 for further study. In the model system, NCGC00229600 inhibited basal and TSH-stimulated cAMP production. NCGC00229600 inhibition of TSH signaling was competitive even though it did not compete for TSH binding; that is, NCGC00229600 is an allosteric inverse agonist. NCGC00229600 inhibited cAMP production by 39 ± 2.6% by all 30 GD sera tested. In primary cultures of human thyrocytes, NCGC00229600 inhibited TSHR-mediated basal and GD sera up-regulation of thyroperoxidase mRNA levels by 65 ± 2.0%. Conclusion: NCGC00229600, a small-molecule allosteric inverse agonist of TSHR, is a general antagonist of TSH receptor activation by TSAbs in GD patient sera. PMID:21123444
A new small-molecule antagonist inhibits Graves' disease antibody activation of the TSH receptor.
Neumann, Susanne; Eliseeva, Elena; McCoy, Joshua G; Napolitano, Giorgio; Giuliani, Cesidio; Monaco, Fabrizio; Huang, Wenwei; Gershengorn, Marvin C
2011-02-01
Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate the TSH receptor (TSHR). We previously reported the first small-molecule antagonist of human TSHR and showed that it inhibited receptor signaling stimulated by sera from four patients with GD. Our objective was to develop a better TSHR antagonist and use it to determine whether inhibition of TSAb activation of TSHR is a general phenomenon. We aimed to chemically modify a previously reported small-molecule TSHR ligand to develop a better antagonist and determine whether it inhibits TSHR signaling by 30 GD sera. TSHR signaling was measured in two in vitro systems: model HEK-EM293 cells stably overexpressing human TSHRs and primary cultures of human thyrocytes. TSHR signaling was measured as cAMP production and by effects on thyroid peroxidase mRNA. We tested analogs of a previously reported small-molecule TSHR inverse agonist and selected the best NCGC00229600 for further study. In the model system, NCGC00229600 inhibited basal and TSH-stimulated cAMP production. NCGC00229600 inhibition of TSH signaling was competitive even though it did not compete for TSH binding; that is, NCGC00229600 is an allosteric inverse agonist. NCGC00229600 inhibited cAMP production by 39 ± 2.6% by all 30 GD sera tested. In primary cultures of human thyrocytes, NCGC00229600 inhibited TSHR-mediated basal and GD sera up-regulation of thyroperoxidase mRNA levels by 65 ± 2.0%. NCGC00229600, a small-molecule allosteric inverse agonist of TSHR, is a general antagonist of TSH receptor activation by TSAbs in GD patient sera.
Nalawade-Chavan, Shweta; McCullagh, James; Hedges, Robert
2014-01-01
Sungir (Russia) is a key Mid-Upper Palaeolithic site in Eurasia, containing several spectacular burials that disclose early evidence for complex burial rites in the form of a range of grave goods deposited along with the dead. Dating has been particularly challenging, with multiple radiocarbon dates ranging from 19,160±270 to 28,800±240 BP for burials that are believed to be closely similar in age. There are disparities in the radiocarbon dates of human bones, faunal remains and charcoal found on the floor of burials. Our approach has been to develop compound-specific methods using High Performance Liquid Chromatography (HPLC) to separate single amino acids, such as hydroxyproline, and thereby avoid the known human contamination on the bones themselves. Previously, we applied this technique to obtain radiocarbon dates of ∼30,000 BP for Sungir 2, Sungir 3 and a mammoth bone from the occupation levels of the site. The single amino acid radiocarbon dates were in good agreement with each other compared to all the dates previously reported, supporting their reliability. Here we report new hydroxyproline dates for two more human burials from the same site, Sungir 1 and Sungir 4. All five hydroxyproline dates reported are statistically indistinguishable and support an identical age for the group. The results suggest that compound-specific radiocarbon analysis should be considered seriously as the method of choice when precious archaeological remains are to be dated because they give a demonstrably contaminant-free radiocarbon age. The new ages are, together with the previously dated 'Red Lady of Paviland' human in the British Isles, the earliest for Mid Upper Palaeolithic burial behaviour in Eurasia, and point to the precocious appearance of this form of rite in Europe Russia.
This report uses results from a previous report titled Assessment of the Impacts of Global Change on Regional U.S. Air Quality: A Synthesis of Climate Change Impacts on Ground-Level Ozone, a number of high-resolution, spatially explicit population projections developed ...
ERIC Educational Resources Information Center
Faughn, Carley; Marrus, Natasha; Shuman, Jeremy; Ross, Stephen R.; Constantino, John N.; Pruett, John R., Jr.; Povinelli, Daniel J.
2015-01-01
Comparative studies of social responsiveness, a core impairment in autism spectrum disorder (ASD), will enhance our understanding of typical and atypical social behavior. We previously reported a quantitative, cross-species (human-chimpanzee) social responsiveness measure, which included the development of the Chimpanzee Social Responsiveness…
González-Barrio, David; Jado, Isabel; Fernández-de-Mera, Isabel G; Del Rocio Fernández-Santos, María; Rodríguez-Vargas, Manuela; García-Amil, Cristina; Beltrán-Beck, Beatriz; Anda, Pedro; Ruiz-Fons, Francisco
2016-06-23
Evidences point to a relevant role of wildlife in the ecology of Coxiella burnetii worldwide. The lack of information on C. burnetii genotypes in wildlife prevents tracing-back clinical animal and human Q fever cases with potential wildlife origin. To compare C. burnetii genotypes circulating in wildlife, livestock and humans, 107 samples from red deer, European wild rabbit, racoon, small mammals, goat and sheep were genotyped by polymerase chain reaction and reverse line blot hybridization. Genomic groups I, II, VI and VII were found in wildlife and groups I, II, III and IV in domestic ruminants. Livestock genotypes clustered mainly with genotypes reported previously in livestock. Genotyping confirmed previous findings that suggest that C. burnetii may display host specificity since most genotypes of sympatric deer and rabbits clustered in separate groups. Wildlife genotypes clustered with genotypes from ticks and from acute hepatitis human Q fever cases, suggesting that particular C. burnetii genotypes circulating in a wildlife-tick cycle may occasionally jump into humans through tick bites or exposure to wildlife. This finding could be behind the reported geographic variation in the clinical presentation of acute Q fever in humans in Spain: atypical pneumonia in the north and hepatitis in the south. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.
The Origin of Malarial Parasites in Orangutans
Pacheco, M. Andreína; Reid, Michael J. C.; Schillaci, Michael A.; Lowenberger, Carl A.; Galdikas, Biruté M. F.; Jones-Engel, Lisa; Escalante, Ananias A.
2012-01-01
Background Recent findings of Plasmodium in African apes have changed our perspectives on the evolution of malarial parasites in hominids. However, phylogenetic analyses of primate malarias are still missing information from Southeast Asian apes. In this study, we report molecular data for a malaria parasite lineage found in orangutans. Methodology/Principal Findings We screened twenty-four blood samples from Pongo pygmaeus (Kalimantan, Indonesia) for Plasmodium parasites by PCR. For all the malaria positive orangutan samples, parasite mitochondrial genomes (mtDNA) and two antigens: merozoite surface protein 1 42 kDa (MSP-142) and circumsporozoite protein gene (CSP) were amplified, cloned, and sequenced. Fifteen orangutans tested positive and yielded 5 distinct mitochondrial haplotypes not previously found. The haplotypes detected exhibited low genetic divergence among them, indicating that they belong to one species. We report phylogenetic analyses using mitochondrial genomes, MSP-142 and CSP. We found that the orangutan malaria parasite lineage was part of a monophyletic group that includes all the known non-human primate malaria parasites found in Southeast Asia; specifically, it shares a recent common ancestor with P. inui (a macaque parasite) and P. hylobati (a gibbon parasite) suggesting that this lineage originated as a result of a host switch. The genetic diversity of MSP-142 in orangutans seems to be under negative selection. This result is similar to previous findings in non-human primate malarias closely related to P. vivax. As has been previously observed in the other Plasmodium species found in non-human primates, the CSP shows high polymorphism in the number of repeats. However, it has clearly distinctive motifs from those previously found in other malarial parasites. Conclusion The evidence available from Asian apes indicates that these parasites originated independently from those found in Africa, likely as the result of host switches from other non-human primates. PMID:22536346
Dawson, Kara L; Bell, Anita; Kawakami, R Pamela; Coley, Kathryn; Yates, Gary; Collins, Desmond M
2012-09-01
Mycobacterium orygis, previously called the oryx bacillus, is a member of the Mycobacterium tuberculosis complex and has been reported only recently as a cause of human tuberculosis in patients of South Asian origin. We present the first case documenting the transmission of this organism from a human to a cow.
ERIC Educational Resources Information Center
Fontenot, Holly B.; Collins Fantasia, Heidi; Charyk, Anna; Sutherland, Melissa A.
2014-01-01
Objective: To examine human papillomavirus (HPV) vaccination rates, including initiation and completion of the vaccine series, and barriers to vaccination in a sample of male college students. Participants: Male students between the ages of 18 and 25 who reported being currently or previously sexually active (N = 735). Methods: A cross-sectional…
In Situ CaptureRT-qPCR: A new simple and sensitive method to detect human norovirus in oysters
USDA-ARS?s Scientific Manuscript database
Human noroviruses (HuNoVs) are the major cause for the non-bacterial acute gastroenteritis worldwide. RT-qPCR is a widely used method to detect HuNoVs. However, the method is unable to discriminate between infectious and non-infectious viruses. Previously, we reported that the receptor mediated in s...
Hennell, Claire; Jamison, Jackie; Wells, Michael; McCluggage, W Glenn
2012-03-01
We report 2 cases of a lesion that we term inverted papilloma of the lower female genital tract, occurring in the cervix and upper vagina of 60- and 50-year-old women, respectively. Microscopically, the features were similar to those of inverted transitional papilloma of the urinary bladder with interconnecting islands, trabeculae, and solid sheets of bland transitional epithelium with an inverted growth pattern. There were small foci of squamous and glandular differentiation in the cervical case. Linear array human papillomavirus genotyping revealed human papillomavirus type 42 in both cases. Inverted papilloma in the lower female genital tract is extremely rare with, as far as we are aware, only 3 previously reported similar cases in the cervix and none in the vagina. Our results suggest that these neoplasms when occurring in the lower female genital tract may be associated with low-risk human papillomavirus, perhaps specifically human papillomavirus 42. Copyright © 2012 Elsevier Inc. All rights reserved.
In Silico Pattern-Based Analysis of the Human Cytomegalovirus Genome
Rigoutsos, Isidore; Novotny, Jiri; Huynh, Tien; Chin-Bow, Stephen T.; Parida, Laxmi; Platt, Daniel; Coleman, David; Shenk, Thomas
2003-01-01
More than 200 open reading frames (ORFs) from the human cytomegalovirus genome have been reported as potentially coding for proteins. We have used two pattern-based in silico approaches to analyze this set of putative viral genes. With the help of an objective annotation method that is based on the Bio-Dictionary, a comprehensive collection of amino acid patterns that describes the currently known natural sequence space of proteins, we have reannotated all of the previously reported putative genes of the human cytomegalovirus. Also, with the help of MUSCA, a pattern-based multiple sequence alignment algorithm, we have reexamined the original human cytomegalovirus gene family definitions. Our analysis of the genome shows that many of the coded proteins comprise amino acid combinations that are unique to either the human cytomegalovirus or the larger group of herpesviruses. We have confirmed that a surprisingly large portion of the analyzed ORFs encode membrane proteins, and we have discovered a significant number of previously uncharacterized proteins that are predicted to be G-protein-coupled receptor homologues. The analysis also indicates that many of the encoded proteins undergo posttranslational modifications such as hydroxylation, phosphorylation, and glycosylation. ORFs encoding proteins with similar functional behavior appear in neighboring regions of the human cytomegalovirus genome. All of the results of the present study can be found and interactively explored online (http://cbcsrv.watson.ibm.com/virus/). PMID:12634390
In silico pattern-based analysis of the human cytomegalovirus genome.
Rigoutsos, Isidore; Novotny, Jiri; Huynh, Tien; Chin-Bow, Stephen T; Parida, Laxmi; Platt, Daniel; Coleman, David; Shenk, Thomas
2003-04-01
More than 200 open reading frames (ORFs) from the human cytomegalovirus genome have been reported as potentially coding for proteins. We have used two pattern-based in silico approaches to analyze this set of putative viral genes. With the help of an objective annotation method that is based on the Bio-Dictionary, a comprehensive collection of amino acid patterns that describes the currently known natural sequence space of proteins, we have reannotated all of the previously reported putative genes of the human cytomegalovirus. Also, with the help of MUSCA, a pattern-based multiple sequence alignment algorithm, we have reexamined the original human cytomegalovirus gene family definitions. Our analysis of the genome shows that many of the coded proteins comprise amino acid combinations that are unique to either the human cytomegalovirus or the larger group of herpesviruses. We have confirmed that a surprisingly large portion of the analyzed ORFs encode membrane proteins, and we have discovered a significant number of previously uncharacterized proteins that are predicted to be G-protein-coupled receptor homologues. The analysis also indicates that many of the encoded proteins undergo posttranslational modifications such as hydroxylation, phosphorylation, and glycosylation. ORFs encoding proteins with similar functional behavior appear in neighboring regions of the human cytomegalovirus genome. All of the results of the present study can be found and interactively explored online (http://cbcsrv.watson.ibm.com/virus/).
Creatinine elevation associated with nitromethane exposure: a marker of potential methanol toxicity.
Cook, Matthew D; Clark, Richard F
2007-10-01
Nitromethane, methanol, and oil are the common components of radio-controlled (R/C) vehicle fuels. Nitromethane can cause a false elevation of serum creatinine concentration as measured by the widely used Jaffe colorimetric method. We gathered data from our poison control system and from previously published case reports to see if a correlation exists between serum methanol concentrations and spuriously elevated serum creatinine concentrations after human exposures to R/C fuel. The California Poison Control System (CPCS) computerized database was queried for all cases of human exposure to R/C vehicle fuel reported between December 1, 2002 and December 1, 2004. Serum creatinine and methanol concentrations were recorded when available, as was the method used to determine serum creatinine. A MEDLINE search was used to obtain previously published cases of human nitromethane exposure associated with falsely elevated creatinine concentrations. During the 2-year period, serum creatinine concentrations were recorded in 7 of 26 R/C fuel exposures (all ingestions), and 6 of these were abnormal (range of 1.9-11.5 mg/dL). In this series, the higher the serum creatinine concentration measured by Jaffe method, the higher the serum methanol concentration. The MEDLINE search yielded data from six previously published case reports on this topic. The data from these case reports seem to follow the trend seen in our case series. These data suggest that a spuriously elevated serum creatinine (by Jaffe method) may have value as an early surrogate marker of methanol poisoning in those who ingest R/C fuel. Also, the degree to which the serum creatinine is elevated may indicate the severity of methanol poisoning.
Infection and Propagation of Human Rhinovirus C in Human Airway Epithelial Cells
Hao, Weidong; Bernard, Katie; Patel, Nita; Ulbrandt, Nancy; Feng, Hui; Svabek, Catherine; Wilson, Susan; Stracener, Christina; Wang, Kathy; Suzich, JoAnn; Blair, Wade
2012-01-01
Human rhinovirus species C (HRV-C) was recently discovered using molecular diagnostic techniques and is associated with lower respiratory tract disease, particularly in children. HRV-C cannot be propagated in immortalized cell lines, and currently sinus organ culture is the only system described that is permissive to HRV-C infection ex vivo. However, the utility of organ culture for studying HRV-C biology is limited. Here, we report that a previously described HRV-C derived from an infectious cDNA, HRV-C15, infects and propagates in fully differentiated human airway epithelial cells but not in undifferentiated cells. We demonstrate that this differentiated epithelial cell culture system supports infection and replication of a second virus generated from a cDNA clone, HRV-C11. We show that HRV-C15 virions preferentially bind fully differentiated airway epithelial cells, suggesting that the block to replication in undifferentiated cells is at the step of viral entry. Consistent with previous reports, HRV-C15 utilizes a cellular receptor other than ICAM-1 or LDLR for infection of differentiated epithelial cells. Furthermore, we demonstrate that HRV-C15 replication can be inhibited by an HRV 3C protease inhibitor (rupintrivir) but not an HRV capsid inhibitor previously under clinical development (pleconaril). The HRV-C cell culture system described here provides a powerful tool for studying the biology of HRV-C and the discovery and development of HRV-C inhibitors. PMID:23035218
Kryazhimskiy, Sergey; Grant, Rebecca; Calcedo, Roberto; Yuan, Xin; Keough, Martin; Sandhu, Arbans; Wang, Qiang; Medina-Jaszek, C. Angelica; Plotkin, Joshua B.; Wilson, James M.
2009-01-01
Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans) and macaques shed substantial quantities of infectious adenoviruses in stool. Shedding in stools from asymptomatic humans was found to be much less frequent, comparable to frequencies reported before. We purified and fully sequenced 30 novel adenoviruses from apes and 3 novel adenoviruses from macaques. Analyses of the new ape adenovirus sequences (as well as the 4 chimpanzee adenovirus sequences we have previously reported) together with 22 complete adenovirus genomes available from GenBank revealed that (a) the ape adenoviruses could clearly be classified into species corresponding to human adenovirus species B, C, and E, (b) there was evidence for intraspecies recombination between adenoviruses, and (c) the high degree of phylogenetic relatedness of adenoviruses across their various primate hosts provided evidence for cross species transmission events to have occurred in the natural history of B and E viruses. The high degree of asymptomatic shedding of live adenovirus in non-human primates and evidence for zoonotic transmissions warrants caution for primate handling and housing. Furthermore, the presence of persistent and/or latent adenovirus infections in the gut should be considered in the design and interpretation of human and non-human primate studies with adenovirus vectors. PMID:19578438
Berseth, C L; Harris, C L; Wampler, J L; Hoffman, D R; Diersen-Schade, D A
2014-09-01
We report the fatty acid composition of mother׳s own human milk from one of the largest US cohorts of lactating mothers of preterm infants. Milk fatty acid data were used as a proxy for intake at enrollment in infants (n=150) who received human milk with a powder human milk fortifier (HMF; Control) or liquid HMF [LHMF; provided additional 12mg docosahexaenoic acid (DHA), 20mg arachidonic acid (ARA)/100mL human milk]. Mothers provided milk samples (n=129) and reported maternal DHA consumption (n=128). Infant blood samples were drawn at study completion (Study Day 28). Human milk and infant PPL fatty acids were analyzed using capillary column gas chromatography. DHA and ARA were within ranges previously published for US term and preterm human milk. Compared to Control HMF (providing no DHA or ARA), human milk fortified with LHMF significantly increased infant PPL DHA and ARA and improved preterm infant DHA and ARA status. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Human Exploration of Mars: The Reference Mission of the NASA Mars Exploration Study Team
NASA Astrophysics Data System (ADS)
Hoffman, Stephen J.; Kaplan, David I.
1997-07-01
Personnel representing several NASA field centers have formulated a "Reference Mission" addressing human exploration of Mars. This report summarizes their work and describes a plan for the first human missions to Mars, using approaches that are technically feasible, have reasonable risks, and have relatively low costs. The architecture for the Mars Reference Mission builds on previous work of the Synthesis Group (1991) and Zubrin's (1991) concepts for the use of propellants derived from the Martian Atmosphere. In defining the Reference Mission, choices have been made. In this report, the rationale for each choice is documented; however, unanticipated technology advances or political decisions might change the choices in the future.
Human Exploration of Mars: The Reference Mission of the NASA Mars Exploration Study Team
NASA Technical Reports Server (NTRS)
Hoffman, Stephen J. (Editor); Kaplan, David I. (Editor)
1997-01-01
Personnel representing several NASA field centers have formulated a "Reference Mission" addressing human exploration of Mars. This report summarizes their work and describes a plan for the first human missions to Mars, using approaches that are technically feasible, have reasonable risks, and have relatively low costs. The architecture for the Mars Reference Mission builds on previous work of the Synthesis Group (1991) and Zubrin's (1991) concepts for the use of propellants derived from the Martian Atmosphere. In defining the Reference Mission, choices have been made. In this report, the rationale for each choice is documented; however, unanticipated technology advances or political decisions might change the choices in the future.
ERIC Educational Resources Information Center
Ribando, Saundra J.; Slade, Catherine P.; Fortner, C. Kevin
2017-01-01
Little research examines the sociocultural aspects of consolidating two post-secondary educational institutions. In a previous study we collected baseline data and reported on the initial impact of consolidation of a research-oriented, health sciences university with a teaching-oriented, comprehensive university. In the study we report here we…
Australian Bat Lyssavirus in a child: the first reported case.
Francis, Joshua R; Nourse, Clare; Vaska, Vikram L; Calvert, Sophie; Northill, Judith A; McCall, Brad; Mattke, Adrian C
2014-04-01
Human infection with Australian Bat Lyssavirus is extremely rare and has not previously been reported in a child. We describe a fatal case of Australian Bat Lyssavirus in an 8-year-old child, and review the literature pertaining to the diagnosis and management of lyssavirus infection with consideration of its applicability to this emerging strain.
Ventriculoperitoneal shunt infection caused by Bifidobacterium breve.
Suwantarat, Nuntra; Romagnoli, Mark; Wakefield, Teresa; Carroll, Karen C
2014-08-01
Bifidobacterium breve is a rare cause of human infections. Previously, bacteremia and meningitis caused by this organism linked to probiotic use have been reported in a neonate. We report the first case of a ventriculoperitoneal shunt infection caused by B. breve in an adult without a history of probiotic use. Copyright © 2014 Elsevier Ltd. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Molecular methods are now more commonly used for identification of the aspergilli and their teleomorphs and have led to reports of species not previously recognized as causing human disease. We report the first case of cerebral aspergillosis in a compromised patient caused by Emericella echinulata,...
Neandertals made the first specialized bone tools in Europe
Soressi, Marie; McPherron, Shannon P.; Lenoir, Michel; Dogandžić, Tamara; Goldberg, Paul; Jacobs, Zenobia; Maigrot, Yolaine; Martisius, Naomi L.; Miller, Christopher E.; Rendu, William; Richards, Michael; Skinner, Matthew M.; Steele, Teresa E.; Talamo, Sahra; Texier, Jean-Pierre
2013-01-01
Modern humans replaced Neandertals ∼40,000 y ago. Close to the time of replacement, Neandertals show behaviors similar to those of the modern humans arriving into Europe, including the use of specialized bone tools, body ornaments, and small blades. It is highly debated whether these modern behaviors developed before or as a result of contact with modern humans. Here we report the identification of a type of specialized bone tool, lissoir, previously only associated with modern humans. The microwear preserved on one of these lissoir is consistent with the use of lissoir in modern times to obtain supple, lustrous, and more impermeable hides. These tools are from a Neandertal context proceeding the replacement period and are the oldest specialized bone tools in Europe. As such, they are either a demonstration of independent invention by Neandertals or an indication that modern humans started influencing European Neandertals much earlier than previously believed. Because these finds clearly predate the oldest known age for the use of similar objects in Europe by anatomically modern humans, they could also be evidence for cultural diffusion from Neandertals to modern humans. PMID:23940333
Crystal structure of the human 4-1BB/4-1BBL complex.
Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel
2018-05-02
4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
Nieto, Amelia; Pozo, Francisco; Vidal-García, Matxalen; Omeñaca, Manuel; Casas, Inmaculada; Falcón, Ana
2017-01-01
Several amino acid changes have been previously implicated in adaptation of avian influenza viruses to human hosts, among them the D701N change in the PB2 polymerase subunit that also is the main determinant of avian virus pathogenesis in animal models. However, previous studies using recombinant viruses did not provide conclusive information of the contribution of this PB2 residue to pathogenicity in human influenza virus strains. We identified this mutation in an A(H1N1)pdm09-like human influenza virus isolated from an infected patient with pneumonia and acute respiratory failure, admitted to the intensive care unit. An exhaustive search has revealed PB2-D701 as a highly conserved position in all available H1N1 human virus sequences in NCBI database, showing a very low prevalence of PB2-D701N change. Presence of PB2-701N amino acid correlates with severe or fatal outcome in those scarce cases with known disease outcome of the infection. In these patients, the residue PB2-701N may contribute to pathogenicity as it was previously reported in humans infected with avian viruses. This study helps to clarify a debate that has arisen regarding the role of PB2-D701N in human influenza virus pathogenicity.
Nieto, Amelia; Pozo, Francisco; Vidal-García, Matxalen; Omeñaca, Manuel; Casas, Inmaculada; Falcón, Ana
2017-01-01
Several amino acid changes have been previously implicated in adaptation of avian influenza viruses to human hosts, among them the D701N change in the PB2 polymerase subunit that also is the main determinant of avian virus pathogenesis in animal models. However, previous studies using recombinant viruses did not provide conclusive information of the contribution of this PB2 residue to pathogenicity in human influenza virus strains. We identified this mutation in an A(H1N1)pdm09-like human influenza virus isolated from an infected patient with pneumonia and acute respiratory failure, admitted to the intensive care unit. An exhaustive search has revealed PB2-D701 as a highly conserved position in all available H1N1 human virus sequences in NCBI database, showing a very low prevalence of PB2-D701N change. Presence of PB2-701N amino acid correlates with severe or fatal outcome in those scarce cases with known disease outcome of the infection. In these patients, the residue PB2-701N may contribute to pathogenicity as it was previously reported in humans infected with avian viruses. This study helps to clarify a debate that has arisen regarding the role of PB2-D701N in human influenza virus pathogenicity. PMID:28421062
Occupational exposure among medical students and house staff at a New York City Medical Center.
Resnic, F S; Noerdlinger, M A
1995-01-09
The purpose of the study was to ascertain the prevalence of and reasons for underreporting of occupational exposures to patients' blood and body fluids among students and house staff. A questionnaire surveyed 110 medical students and 275 house staff members regarding the number of reported and unreported exposures to patients' body fluids, and the reasons why the respondents did or did not report their exposures during the previous 6 months. Of 385 surveys returned, representing a response rate of 60%, 122 respondents (32%) experienced 330 occupational exposures during the previous 6 months. Fifty-two percent of surgical house staff, 27% of students, and 20% of medical house staff were exposed. Whereas the exposure risk to surgical house staff increased with training, the risk to medical house staff decreased with training. Only 29% of exposed respondents reported an exposure. Exposures from sources known to be positive or at high risk for human immunodeficiency virus had the highest reporting rates. The most frequent reason for not reporting an exposure was that the patient was thought not to be infectious. Forty-six percent of respondents exposed to sources of unknown human immunodeficiency virus status who did not report chose "patient thought not to be infectious" as the reason. The most common reason for reporting an exposure was "hospital policy." Although limited by recall bias, this study showed that a high proportion of students and house staff experience occupational exposures. The results suggest that populations at high risk for exposures are the more experienced surgical house staff and the junior medical house staff. Exposures from sources known to be positive or at high risk for human immunodeficiency virus were reported more frequently than those from unknown risk sources.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1988-09-30
The William Dick Lagoon site consists of three unlined lagoons (approximately 2.5 acres total area) which previously contained over four million gallons of rinse water from cleaning chemical tank trailers. In 1970, two of the lagoons breached and released approximately 300,000 gallons of wastewater into the nearby area and a small tributary. Trichloroethylene, toluene, 4,4-DDE, and polynuclear aromatic hydrocarbons have been reported in the soil on the site. Trichloroethylene was detected in a nearby spring, previously used as a water source by a small number of residents. Potential human exposure pathways include ingestion of contaminated water, dermal exposure to contaminatedmore » water and soil, and inhalation of contaminated dust and organics in the contaminated groundwater. The site is considered to be of potential public health concern because of the risk to human health caused by the possibility of exposure to hazardous substances. However, it does not appear that a human population is currently exposed to site contaminants at levels of health concern.« less
Calcium Kinetics During Long-Duration Space Flight
NASA Technical Reports Server (NTRS)
Smith, Scott M.; OBrien, K. O.; Wastney, M. E.; Morukov, B. V.; Larina, I.; Abrams, S. A.; Lane, H. W.; Nillen, J. L.; Davis-Street, J. E.; Oganov, V.;
2001-01-01
Bone loss represents one of the most significant effects of space flight on the human body. Understanding the mechanisms underlying this loss is critical for maintaining crew health and safety during and after flight. This investigation documents the changes in bone metabolism and calcium kinetics during and after space flight. We previously reported calcium studies on three subjects during and after a 115-d stay on the Russian space station Mir. We report here data on an additional three subjects, whose stays on Mir were approximately 4 (n=l) and 6 (n=2) mos. Previously published data are included for comparison.
American cutaneous leishmaniasis triggered by electrocoagulation.
Martins, Sofia Sales; Santos, Adriana de Oliveira; Lima, Beatriz Dolabela; Gomes, Ciro Martins; Sampaio, Raimunda Nonata Ribeiro
2018-01-01
Cutaneous leishmaniasis is usually transmitted by infected phlebotomine sand fly bites that initiate local cutaneous lesions. Few reports in the literature describe other modes of transmission. We report a case of a previously healthy 59-year-old woman who underwent electrocoagulation to remove seborrheic keratosis confirmed by dermatoscopy. Three months later, a skin fragment tested positive for Leishmania culture; the parasite was identified as L. (V.) braziliensis. Trauma may generate inflammatory cascades that favor Leishmania growth and lesion formation in previously infected patients. American cutaneous leishmaniasis is a dynamic disease with unclear pathophysiology because of continually changing environments, demographics, and human behaviors.
ERIC Educational Resources Information Center
Kral, Paul A.; And Others
Investigates the effect of delay of reinforcement upon human discrimination learning with particular emphasis on the form of the gradient within the first few seconds of delay. In previous studies subjects are usually required to make an instrumental response to a stimulus, this is followed by the delay interval, and finally, the reinforcement…
USDA-ARS?s Scientific Manuscript database
Human noroviruses (HuNoVs) are major agents of gastroenteritis and water is an important route of transmission. Using magnetic beads conjugated with blood group-like antigens previously reported as receptors for HuNoV, we developed a simple and rapid receptor-binding capture and magnetic sequestra...
Cooling Rates of Humans in Air and in Water: An Experiment
NASA Astrophysics Data System (ADS)
Bohren, Craig F.
2012-12-01
In a previous article I analyzed in detail the physical factors resulting in greater cooling rates of objects in still water than in still air, emphasizing cooling of the human body. By cooling rate I mean the rate of decrease of core temperature uncompensated by metabolism. I concluded that the "correct ratio for humans is closer to 2 than to 10." To support this assertion I subsequently did experiments, which I report following a digression on hypothermia.
Rosman, Raihana; Saifullah, Bullo; Maniam, Sandra; Dorniani, Dena; Hussein, Mohd Zobir; Fakurazi, Sharida
2018-02-02
Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe₃O₄-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe₃O₄-PEG) nanocarrier and of anticancer nanocomposite (Fe₃O₄-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe₃O₄-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies.
Stein, R A
2015-01-01
On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea. Human infections shortly emerged in Liberia, Sierra Leone, and Nigeria. On 30 September 2014, the Centers for Disease Control and Prevention confirmed through laboratory testing the first Ebola virus infection diagnosed in the USA, in a patient who travelled from West Africa to Texas. On 6 October 2014, the first human infection occurring outside of Africa was reported, in a Spanish nurse who treated two priests, both of whom died, and on 23 October 2014, the first human infection was reported in New York City. To date, the 2014 Ebola virus outbreak is the longest, largest, and most persistent one since 1976, when the virus was first identified in humans, and the number of human cases exceeded, as of mid-September 2014, the cumulative number of infections from all the previous outbreaks. The early clinical presentation overlaps with other infectious diseases, opening differential diagnosis difficulties. Understanding the transmission routes and identifying the natural reservoir of the virus are additional challenges in studying Ebola hemorrhagic fever outbreaks. Ebola virus is as much a public health challenge for developing countries as it is for the developed world, and previous outbreaks underscored that the relative contribution of the risk factors may differ among outbreaks. The implementation of effective preparedness plans is contingent on integrating teachings from previous Ebola virus outbreaks with those from the current outbreak and with lessons provided by other infectious diseases, along with developing a multifaceted inter-disciplinary and cross-disciplinary framework that should be established and shaped by biomedical as well as sociopolitical sciences. © 2014 John Wiley & Sons Ltd.
T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.
Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F
2016-09-01
TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.
USDA-ARS?s Scientific Manuscript database
The existence of two separate lineages of Escherichia coli O157:H7 has previously been reported, and research indicates that lineage I might be more pathogenic towards human hosts than lineage II. We have previously shown that lineage I expresses higher levels of Shiga toxin 2 (Stx2). To evaluate w...
Luethi, Dino; Liechti, Matthias E
2018-05-29
Pharmacological profiles of new psychoactive substances (NPSs) can be established rapidly in vitro and provide information on potential psychoactive effects in humans. The present study investigated whether specific in vitro monoamine transporter and receptor interactions can predict effective psychoactive doses in humans. We correlated previously assessed in vitro data of stimulants and psychedelics with human doses that are reported on the Internet and in books. For stimulants, dopamine and norepinephrine transporter inhibition potency was positively correlated with human doses, whereas serotonin transporter inhibition potency was inversely correlated with human doses. Serotonin 5-hydroxytryptamine-2A (5-HT2A) and 5-HT2C receptor affinity was significantly correlated with psychedelic doses, but 5-HT1A receptor affinity and 5-HT2A and 5-HT2B receptor activation potency were not. The rapid assessment of in vitro pharmacological profiles of NPSs can help to predict psychoactive doses and effects in humans and facilitate the appropriate scheduling of NPSs.
Fan, Xiaobo; Supiwong, Weerayuth; Weise, Anja; Mrasek, Kristin; Kosyakova, Nadezda; Tanomtong, Alongkoad; Pinthong, Krit; Trifonov, Vladimir A; Cioffi, Marcelo de Bello; Grothmann, Pierre; Liehr, Thomas; Oliveira, Edivaldo H C de
2015-11-01
Comparative cytogenetic analysis in New World Monkeys (NWMs) using human multicolor banding (MCB) probe sets were not previously done. Here we report on an MCB based FISH-banding study complemented with selected locus-specific and heterochromatin specific probes in four NWMs and one Old World Monkey (OWM) species, i.e. in Alouatta caraya (ACA), Callithrix jacchus (CJA), Cebus apella (CAP), Saimiri sciureus (SSC), and Chlorocebus aethiops (CAE), respectively. 107 individual evolutionary conserved breakpoints (ECBs) among those species were identified and compared with those of other species in previous reports. Especially for chromosomal regions being syntenic to human chromosomes 6, 8, 9, 10, 11, 12 and 16 previously cryptic rearrangements could be observed. 50.4% (54/107) NWM-ECBs were colocalized with those of OWMs, 62.6% (62/99) NWM-ECBs were related with those of Hylobates lar (HLA) and 66.3% (71/107) NWM-ECBs corresponded with those known from other mammalians. Furthermore, human fragile sites were aligned with the ECBs found in the five studied species and interestingly 66.3% ECBs colocalized with those fragile sites (FS). Overall, this study presents detailed chromosomal maps of one OWM and four NWM species. This data will be helpful to further investigation on chromosome evolution in NWM and hominoids in general and is prerequisite for correct interpretation of future sequencing based genomic studies in those species.
Magnetoacoustic imaging of human liver tumor with magnetic induction
NASA Astrophysics Data System (ADS)
Hu, Gang; Cressman, Erik; He, Bin
2011-01-01
Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.
Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhu, Xueyong; Viswanathan, Karthik; Raman, Rahul
Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Viet Nam/1203/04 and A/Indonesia/5/05 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6 linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3 linked sialosides.more » Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogues reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.« less
Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants
Zhu, Xueyong; Viswanathan, Karthik; Raman, Rahul; ...
2015-11-01
Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Viet Nam/1203/04 and A/Indonesia/5/05 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6 linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3 linked sialosides.more » Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogues reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.« less
Heibeck, Tyler H.; Ding, Shi-Jian; Opresko, Lee K.; Zhao, Rui; Schepmoes, Athena A.; Yang, Feng; Tolmachev, Aleksey V.; Monroe, Matthew E.; Camp, David G.; Smith, Richard D.; Wiley, H. Steven; Qian, Wei-Jun
2010-01-01
Protein tyrosine phosphorylation represents a central regulatory mechanism in cell signaling. Here we present an extensive survey of tyrosine phosphorylation sites in a normal-derived human mammary epithelial cell line by applying anti-phosphotyrosine peptide immunoaffinity purification coupled with high sensitivity capillary liquid chromatography tandem mass spectrometry. A total of 481 tyrosine phosphorylation sites (covered by 716 unique peptides) from 285 proteins were confidently identified in HMEC following the analysis of both the basal condition and acute stimulation with epidermal growth factor (EGF). The estimated false discovery rate was 1.0% as determined by searching against a scrambled database. Comparison of these data with existing literature showed significant agreement for previously reported sites. However, we observed 281 sites that were not previously reported for HMEC cultures and 29 of which have not been reported for any human cell or tissue system. The analysis showed that the majority of highly phosphorylated proteins were relatively low-abundance. Large differences in phosphorylation stoichiometry for sites within the same protein were also observed, raising the possibility of more important functional roles for such highly phosphorylated pTyr sites. By mapping to major signaling networks, such as the EGF receptor and insulin growth factor-1 receptor signaling pathways, many known proteins involved in these pathways were revealed to be tyrosine phosphorylated, which provides interesting targets for future hypothesis-driven and targeted quantitative studies involving tyrosine phosphorylation in HMEC or other human systems. PMID:19534553
Purty, Shashikala; Saranathan, Rajagopalan; Prashanth, K; Narayanan, K; Asir, Johny; Sheela Devi, Chandrakesan; Kumar Amarnath, Satish
2013-01-01
Although not previously known to cause human infections, Kocuria species have now emerged as human pathogens, mostly in compromised hosts with severe underlying disease. Recently, there has been an increasing incidence of different types of Kocuria infections reported, most likely due to the adoption of better identification methods. Here, we report a case of peritonitis caused by Kocuria rosea in a diabetic nephropathy patient who was on continuous ambulatory peritoneal dialysis. Sepsis and peritonitis caused by K. rosea in our case yielded two identical Kocuria isolates from the peritoneal dialysate fluid within a period of three days. The infection was subsequently resolved by antibiotic treatment and catheter removal. In addition to reporting this case, we herein review the literature concerning the emergence of Kocuria as a significant human pathogen. The majority of cases were device-related, acquired in the hospital or endogenous, and different Kocuria species appear to share a common etiology of peritonitis. The overall disease burden associated with Kocuria appears to be high, and the treatment guidelines for diseases associated with Kocuria have not yet been clearly defined. PMID:26038440
NASA Technical Reports Server (NTRS)
Leong, J.; Hughes-Fulford, M.; Rakhlin, N.; Habib, A.; Maclouf, J.; Goldyne, M. E.
1996-01-01
Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published.
Morningness-Eveningness and Satisfaction with Life
ERIC Educational Resources Information Center
Randler, Christoph
2008-01-01
Individual differences in diurnal preferences and circadian rhythms are viewed as an interesting dimension of human personality. Previous research has examined various psychological correlates of diurnal preference. Evening types reported psychological and psychosomatic disturbances more frequently and intensively than morning types and morning…
Human furuncular myiasis caused by Hermetia illucens (Diptera: Stratiomyidae).
Adler, A I; Brancato, F P
1995-09-01
Cutaneous myiasis caused by Hermetia illucens (L.) has not been reported previously. We present a case of facultative furuncular myiasis characterized by infestation with a single larva in a woman from Seattle, WA, who had traveled to East Africa.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dichgans, M.; Mayer, M.; Straube, A.
1996-02-15
This article reports on new information regarding the genetic mapping of the human CADASIL gene region. Previously, the gene had been mapped to human chromosome 19q12. Using the identification of a chromosomal crossover, the region has been refined to an 8-cM interval. 11 refs., 2 figs., 1 tab.
Understanding and Addressing Cultural Variation in Costly Antisocial Punishment
2012-08-15
explanation for cooperation. Here too though the reasoning seemed cyclic, as punishment was a form of altruism itself. Due to previous research on human ...14. ABSTRACT This report results from a contract tasking University of Bath as follows: The varieties of human cultures are a rich treasure...significantly more altruistic than the punisher, even though the punisher benefits from their altruism . The results of this research project
Effect of lipophilicity modulation on inhibition of human rhinovirus capsid binders.
Morley, Andrew; Tomkinson, Nicholas; Cook, Andrew; MacDonald, Catherine; Weaver, Richard; King, Sarah; Jenkinson, Lesley; Unitt, John; McCrae, Christopher; Phillips, Tim
2011-10-15
To try and generate broad spectrum human rhinovirus VP1 inhibitors with more attractive physicochemical, DMPK and safety profiles, we explored the current SAR of known VP1 compounds. This lead to the identification of specific structural regions where reduction in polarity can be achieved, so guiding chemistry to analogues with significantly superior profiles to previously reported inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.
Fetal myosin immunoreactivity in human dystrophic muscle.
Schiaffino, S; Gorza, L; Dones, I; Cornelio, F; Sartore, S
1986-01-01
We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.
Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rocke, David
2016-08-01
In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.
Béraud-Colomb, E; Roubin, R; Martin, J; Maroc, N; Gardeisen, A; Trabuchet, G; Goosséns, M
1995-12-01
Analyzing the nuclear DNA from ancient human bones is an essential step to the understanding of genetic diversity in current populations, provided that such systematic studies are experimentally feasible. This article reports the successful extraction and amplification of nuclear DNA from the beta-globin region from 5 of 10 bone specimens up to 12,000 years old. These have been typed for beta-globin frameworks by sequencing through two variable positions and for a polymorphic (AT) chi (T) gamma microsatellite 500 bp upstream of the beta-globin gene. These specimens of human remains are somewhat older than those analyzed in previous nuclear gene sequencing reports and considerably older than those used to study high-copy-number human mtDNA. These results show that the systematic study of nuclear DNA polymorphisms of ancient populations is feasible.
Functional impact of the human mobilome.
Babatz, Timothy D; Burns, Kathleen H
2013-06-01
The human genome is replete with interspersed repetitive sequences derived from the propagation of mobile DNA elements. Three families of human retrotransposons remain active today: LINE1, Alu, and SVA elements. Since 1988, de novo insertions at previously recognized disease loci have been shown to generate highly penetrant alleles in Mendelian disorders. Only recently has the extent of germline-transmitted retrotransposon insertion polymorphism (RIP) in human populations been fully realized. Also exciting are recent studies of somatic retrotransposition in human tissues and reports of tumor-specific insertions, suggesting roles in tissue heterogeneity and tumorigenesis. Here we discuss mobile elements in human disease with an emphasis on exciting developments from the last several years. Copyright © 2013 Elsevier Ltd. All rights reserved.
Tanimura, Akira; Dan, Shingo; Yoshida, Mitsuaki
1998-01-01
The expression of human T-cell leukemia virus type 1 (HTLV-1) is activated by interaction of a viral transactivator protein, Tax, and cellular transcription factor, CREB (cyclic AMP response element binding protein), which bind to a 21-bp enhancer in the long terminal repeats (LTR). THP (Tax-helping protein) was previously determined to enhance the transactivation by Tax protein. Here we report novel forms of the human homolog of a member of the Gli oncogene family, Gli2 (also termed Gli2/THP), an extended form of a zinc finger protein, THP, which was described previously. Four possible isoforms (hGli2 α, β, γ, and δ) are formed by combinations of two independent alternative splicings, and all the isoforms could bind to a DNA motif, TRE2S, in the LTR. The longer isoforms, α and β, were abundantly expressed in various cell lines including HTLV-1-infected T-cell lines. Fusion proteins of the hGli2 isoforms with the DNA-binding domain of Gal4 activated transcription when the reporter contained a Gal4-binding site and one copy of the 21-bp sequence, to which CREB binds. This activation was observed only in the presence of Tax. The 21-bp sequence in the reporter was also essential for the activation. These results suggest that simultaneous binding of hGli2 and CREB to the respective sites in the reporter seems to be critical for Tax protein to activate transcription. Consequently, it is probable that the LTR can be regulated by two independent signals through hGli2 and CREB, since the LTR contains the 21-bp and TRE2S sequences in the vicinity. PMID:9557682
Tilgner, Katarzyna; Atkinson, Stuart P; Yung, Sun; Golebiewska, Anna; Stojkovic, Miodrag; Moreno, Ruben; Lako, Majlinda; Armstrong, Lyle
2010-01-01
The isolation of significant numbers of human primordial germ cells at several developmental stages is important for investigations of the mechanisms by which they are able to undergo epigenetic reprogramming. Only small numbers of these cells can be obtained from embryos of appropriate developmental stages, so the differentiation of human embryonic stem cells is essential to obtain sufficient numbers of primordial germ cells to permit epigenetic examination. Despite progress in the enrichment of human primordial germ cells using fluorescence-activated cell sorting (FACS), there is still no definitive marker of the germ cell phenotype. Expression of the widely conserved RNA helicase VASA is restricted to germline cells, but in contrast to species such as Mus musculus in which reporter constructs expressing green fluorescent protein (GFP) under the control of a Vasa promoter have been developed, such reporter systems are lacking in human in vitro models. We report here the generation and characterization of human embryonic stem cell lines stably carrying a VASA-pEGFP-1 reporter construct that expresses GFP in a population of differentiating human embryonic stem cells that show expression of characteristic markers of primordial germ cells. This population shows a different pattern of chromatin modifications to those obtained by FACS enrichment of Stage Specific Antigen one expressing cells in our previous publication.
MECHANISMS OF NANODIAMOND PARTICLE INDUCED IL-8 EXPRESSION IN HUMAN AIRWAY EPITHELIAL CELLS
Nanodiamond particles (NDP) prepared by detonation under confined conditions have a number of industrial and analytical applications. Previous in vitro studies have reported NDP to be biologically inert with negligible cytotoxicity, implying that they are potentially suitable for...
The Climate Science Special Report: Detection and Attribution
NASA Astrophysics Data System (ADS)
Wehner, M. F.
2017-12-01
The Climate Science Special Report reiterates previous findings about the human influence on global mean surface air temperature with the statement "…it is extremely likely that human activities, especially emissions of greenhouse gases, are the dominant cause of the observed warming since the mid 20th century. For the warming over the last century, there is no convincing alternative explanation supported by the extent of the observational evidence." This is a statement made with high confidence and supported by multiple lines of evidence. The report also assesses the latest developments in the field of probabilistic extreme event attribution—the quantification of the influence of anthropogenic climate change on individual extreme weather events—with a focus on those recent events within the United States that have been analyzed. Thirty different events within the US are reported on including heat waves, cold snaps, wet seasons, individual storms and droughts. Most but not all of the individual US events studied revealed an influence from human induced changes to the climate system.
Environmental Hazards Assessment Program. Quarterly report, January 1994--March 1994
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1994-05-04
The objectives of the EHAP program are to: Develop a holistic, national basis for risk assessment, risk management and risk communication; Develop a pool of talented scientists and experts in cleanup activities, especially in human health aspects, and; Identify needs and develop programs addressing the critical shortage of well-educated, highly-skilled technical and scientific personnel to address the health oriented aspects of environmental restoration and waste management. This report describes activities and reports on progress for the third quarter of year two (January-March, 1994) of the grant. To better accomplish objectives, grant efforts are organized into three major elements: The Crossroadsmore » of Humanity Series; Research, Science and Education Programs; and Program Management. The Crossroads of Humanity Series charted a new course, incorporating lessons learned during previous quarters into a series of programs designed to address environmental issues in a real world setting. Reports are included on the various research programs with milestones and deliverables from the third quarter.« less
Keller, Peter M.; Rampini, Silvana K.; Büchler, Andrea C.; Eich, Gerhard; Wanner, Roger M.; Speck, Roberto F.; Böttger, Erik C.; Bloemberg, Guido V.
2010-01-01
Clinical isolates that are difficult to identify by conventional means form a valuable source of novel human pathogens. We report on a 5-year study based on systematic 16S rRNA gene sequence analysis. We found 60 previously unknown 16S rRNA sequences corresponding to potentially novel bacterial taxa. For 30 of 60 isolates, clinical relevance was evaluated; 18 of the 30 isolates analyzed were considered to be associated with human disease. PMID:20631113
Pimentel, Jason D; Mahadevan, Kumar; Woodgyer, Alan; Sigler, Lynne; Gibas, Connie; Harris, Owen C; Lupino, Michael; Athan, Eugene
2005-08-01
Fungal peritonitis due to Curvularia species in patients undergoing peritoneal dialysis is a very rare problem. We report a case of peritonitis caused by Curvularia inaequalis. This is the first report in the English literature of this species causing human infection. We also review the six previously reported cases of continuous ambulatory peritoneal dialysis peritonitis caused by other Curvularia species.
Shalhoub, Sarah; AlZahrani, Abdulwahab; Simhairi, Raed; Mushtaq, Adnan
2015-01-01
Middle East Respiratory Syndrome Coronavirus (MERS CoV) may cause severe pneumonia with significant morbidity and mortality, particularly in patients with multiple comorbid condition. MERS CoV pneumonia has not been previously reported in patients with Human Immunodeficiency Virus (HIV). Herein, we report a case of MERS CoV pneumonia with a successful outcome in a patient recently diagnosed with HIV. Copyright © 2014 Elsevier B.V. All rights reserved.
Differentiation between decomposed remains of human origin and bigger mammals.
Rosier, E; Loix, S; Develter, W; Van de Voorde, W; Cuypers, E; Tytgat, J
2017-08-01
This study is a follow-up study in the search for a human specific marker in the decomposition where the VOC-profile of decomposing human, pig, lamb and roe remains were analyzed using a thermal desorber combined with a gas chromatograph coupled to a mass spectrometer in a laboratory environment during 6 months. The combination of 8 previously identified human and pig specific compounds (ethyl propionate, propyl propionate, propyl butyrate, ethyl pentanoate, 3-methylthio-1-propanol, methyl(methylthio)ethyl disulfide, diethyl disulfide and pyridine) was also seen in these analyzed mammals. However, combined with 5 additional compounds (hexane, heptane, octane, N-(3-methylbutyl)- and N-(2-methylpropyl)acetamide) human remains could be separated from pig, lamb and roe remains. Based on a higher number of remains analyzed, as compared with the pilot study, it was no longer possible to rely on the 5 previously proposed esters to separate pig from human remains. From this follow-up study reported, it was found that pyridine is an interesting compound specific to human remains. Such a human specific marker can help in the training of cadaver dogs or in the development of devices to search for human remains. However, further investigations have to verify these results. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
A Proteome-wide Fission Yeast Interactome Reveals Network Evolution Principles from Yeasts to Human.
Vo, Tommy V; Das, Jishnu; Meyer, Michael J; Cordero, Nicolas A; Akturk, Nurten; Wei, Xiaomu; Fair, Benjamin J; Degatano, Andrew G; Fragoza, Robert; Liu, Lisa G; Matsuyama, Akihisa; Trickey, Michelle; Horibata, Sachi; Grimson, Andrew; Yamano, Hiroyuki; Yoshida, Minoru; Roth, Frederick P; Pleiss, Jeffrey A; Xia, Yu; Yu, Haiyuan
2016-01-14
Here, we present FissionNet, a proteome-wide binary protein interactome for S. pombe, comprising 2,278 high-quality interactions, of which ∼ 50% were previously not reported in any species. FissionNet unravels previously unreported interactions implicated in processes such as gene silencing and pre-mRNA splicing. We developed a rigorous network comparison framework that accounts for assay sensitivity and specificity, revealing extensive species-specific network rewiring between fission yeast, budding yeast, and human. Surprisingly, although genes are better conserved between the yeasts, S. pombe interactions are significantly better conserved in human than in S. cerevisiae. Our framework also reveals that different modes of gene duplication influence the extent to which paralogous proteins are functionally repurposed. Finally, cross-species interactome mapping demonstrates that coevolution of interacting proteins is remarkably prevalent, a result with important implications for studying human disease in model organisms. Overall, FissionNet is a valuable resource for understanding protein functions and their evolution. Copyright © 2016 Elsevier Inc. All rights reserved.
Arenas, Ailan F; Salcedo, Gladys E; Gomez-Marin, Jorge E
2017-01-01
Pathogen-host protein-protein interaction systems examine the interactions between the protein repertoires of 2 distinct organisms. Some of these pathogen proteins interact with the host protein system and may manipulate it for their own advantages. In this work, we designed an R script by concatenating 2 functions called rowDM and rowCVmed to infer pathogen-host interaction using previously reported microarray data, including host gene enrichment analysis and the crossing of interspecific domain-domain interactions. We applied this script to the Toxoplasma-host system to describe pathogen survival mechanisms from human, mouse, and Toxoplasma Gene Expression Omnibus series. Our outcomes exhibited similar results with previously reported microarray analyses, but we found other important proteins that could contribute to toxoplasma pathogenesis. We observed that Toxoplasma ROP38 is the most differentially expressed protein among toxoplasma strains. Enrichment analysis and KEGG mapping indicated that the human retinal genes most affected by Toxoplasma infections are those related to antiapoptotic mechanisms. We suggest that proteins PIK3R1, PRKCA, PRKCG, PRKCB, HRAS, and c-JUN could be the possible substrates for differentially expressed Toxoplasma kinase ROP38. Likewise, we propose that Toxoplasma causes overexpression of apoptotic suppression human genes. PMID:29317802
Thyroid hormones (TH) play crucial roles in brain maturation, neuronal migration, and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported...
PFIESTERIA PISCICIDA-INDUCED COGNITIVE EFFECTS: VISUAL SIGNAL DETECTION PERFORMANCE AND REVERSAL.
Humans exposed to Pfiesteria piscicida report cognitive impairment. In a rat model, we showed that exposure to Pfiesteria impaired learning a new task, but not performance of previously-learned behavior. In this study, we characterized the behavioral effects of Pfiesteria in rats...
ALTERED MAMMARY GLAND DEVELOPMENT IN MALE RATS EXPOSED TO GENISTEIN AND METHOXYCHLOR
Genistein is a prevalent phytoestrogen whose presence in human and animal foods may affect biological actions of synthetic endocrine active compounds. We have previously reported that in utero and lactational exposure to genistein and the endocrine active pesticide methoxychlor c...
The cyanobacteria toxins, microcystins – emerging risks to human health
Dialysis patients appear to be at increased risk for exposure to cyanobacteria toxins; episodes of microcystin (MCYST) exposure via dialysate during 1996 and 2001 have been previously reported. During 2001, as many as 44 renal insufficiency patients were exposed to contaminated d...
Reappraisal of known malaria resistance loci in a large multi-centre study
Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.
2015-01-01
Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. PMID:25261933
Tse, Herman; Tsoi, Hoi-Wah; Teng, Jade L. L.; Chen, Xin-Chun; Liu, Haiying; Zhou, Boping; Zheng, Bo-Jian; Woo, Patrick C. Y.; Lau, Susanna K. P.; Yuen, Kwok-Yung
2011-01-01
Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively). In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China. These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples. One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype. The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses. The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2. Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae. PMID:21980506
Godreuil, Sylvain; Didelot, Marie-Noëlle; Perez, Colette; Leflèche, Anne; Boiron, Patrick; Reynes, Jacques; Laurent, Frédéric; Jean-Pierre, Hélène; Marchandin, Hélène
2003-01-01
Nocardia veterana is a recently characterized species within the genus Nocardia, and only three human clinical isolates have been reported for this species. We describe a case of ascitic fluid infection in an immunocompromised patient due to N. veterana. To our knowledge, this is the first report of a Nocardia sp. strain from ascitic fluid and the fourth report of N. veterana isolated from human samples. Chemotaxonomic methods showed the strain to belong to the genus Nocardia, and identification to the species level was done by 16S ribosomal DNA gene sequencing. The antibiotic susceptibility profile of N. veterana is reported here for the second time. The strain was deposited in the Collection of the Pasteur Institute and in the Culture Collection of the University of Göteborg (CIP 107497 and CCUG 46576). The corresponding 16S ribosomal DNA gene sequence is available from the GenBank database under accession number AY149599. A phylogenetic analysis was conducted and showed that N. veterana was most closely related to the recently characterized species Nocardia africana rather than to Nocardia vaccinii, as previously reported. PMID:12791927
Behaviorally Relevant Abstract Object Identity Representation in the Human Parietal Cortex
Jeong, Su Keun
2016-01-01
The representation of object identity is fundamental to human vision. Using fMRI and multivoxel pattern analysis, here we report the representation of highly abstract object identity information in human parietal cortex. Specifically, in superior intraparietal sulcus (IPS), a region previously shown to track visual short-term memory capacity, we found object identity representations for famous faces varying freely in viewpoint, hairstyle, facial expression, and age; and for well known cars embedded in different scenes, and shown from different viewpoints and sizes. Critically, these parietal identity representations were behaviorally relevant as they closely tracked the perceived face-identity similarity obtained in a behavioral task. Meanwhile, the task-activated regions in prefrontal and parietal cortices (excluding superior IPS) did not exhibit such abstract object identity representations. Unlike previous studies, we also failed to observe identity representations in posterior ventral and lateral visual object-processing regions, likely due to the greater amount of identity abstraction demanded by our stimulus manipulation here. Our MRI slice coverage precluded us from examining identity representation in anterior temporal lobe, a likely region for the computing of identity information in the ventral region. Overall, we show that human parietal cortex, part of the dorsal visual processing pathway, is capable of holding abstract and complex visual representations that are behaviorally relevant. These results argue against a “content-poor” view of the role of parietal cortex in attention. Instead, the human parietal cortex seems to be “content rich” and capable of directly participating in goal-driven visual information representation in the brain. SIGNIFICANCE STATEMENT The representation of object identity (including faces) is fundamental to human vision and shapes how we interact with the world. Although object representation has traditionally been associated with human occipital and temporal cortices, here we show, by measuring fMRI response patterns, that a region in the human parietal cortex can robustly represent task-relevant object identities. These representations are invariant to changes in a host of visual features, such as viewpoint, and reflect an abstract level of representation that has not previously been reported in the human parietal cortex. Critically, these neural representations are behaviorally relevant as they closely track the perceived object identities. Human parietal cortex thus participates in the moment-to-moment goal-directed visual information representation in the brain. PMID:26843642
Distinct human antibody response to the biological warfare agent Burkholderia mallei.
Varga, John J; Vigil, Adam; DeShazer, David; Waag, David M; Felgner, Philip; Goldberg, Joanna B
2012-10-01
The genetic similarity between Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. In 2000, the first human case of glanders in North America since 1945 was reported in a microbiology laboratory worker. Leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohort of melioidosis patients in southeast Asia, we describe the antibody response in a human with glanders. Analysis of 156 peptides present on the array revealed antibodies against 17 peptides with a > 2-fold increase in this infection. Unexpectedly, when the glanders data were compared with a previous data set from B. pseudomallei infections, there were only two highly increased antibodies shared between these two infections. These findings have implications in the diagnosis and treatment of B. mallei and B. pseudomallei infections.
The effect of spaceflight and microgravity on the human brain.
Van Ombergen, Angelique; Demertzi, Athena; Tomilovskaya, Elena; Jeurissen, Ben; Sijbers, Jan; Kozlovskaya, Inessa B; Parizel, Paul M; Van de Heyning, Paul H; Sunaert, Stefan; Laureys, Steven; Wuyts, Floris L
2017-10-01
Microgravity, confinement, isolation, and immobilization are just some of the features astronauts have to cope with during space missions. Consequently, long-duration space travel can have detrimental effects on human physiology. Although research has focused on the cardiovascular and musculoskeletal system in particular, the exact impact of spaceflight on the human central nervous system remains to be determined. Previous studies have reported psychological problems, cephalic fluid shifts, neurovestibular problems, and cognitive alterations, but there is paucity in the knowledge of the underlying neural substrates. Previous space analogue studies and preliminary spaceflight studies have shown an involvement of the cerebellum, cortical sensorimotor, and somatosensory areas and the vestibular pathways. Extending this knowledge is crucial, especially in view of long-duration interplanetary missions (e.g., Mars missions) and space tourism. In addition, the acquired insight could be relevant for vestibular patients, patients with neurodegenerative disorders, as well as the elderly population, coping with multisensory deficit syndromes, immobilization, and inactivity.
Manning, Lois R.; Popowicz, Anthony M.; Padovan, Julio C.; Chait, Brian T.; Manning, James M.
2016-01-01
This report establishes a correlation between two known properties of the human embryonic hemoglobins-- their weak subunit assemblies as demonstrated here by gel filtration at very dilute protein concentrations and their high oxygen affinities and reduced cooperativities reported previously by others but without a mechanistic basis. We demonstrate here that their high oxygen affinities are a consequence of their weak assemblies. Weak vs strong hemoglobin tetramers represent a regulatory mechanism to modulate oxygen binding capacity by altering the equilibrium between the various steps in the assembly process that can be described as an inverse allosteric effect. PMID:27965062
Manning, Lois R; Popowicz, Anthony M; Padovan, Julio C; Chait, Brian T; Manning, James M
2017-02-15
This report establishes a correlation between two known properties of the human embryonic hemoglobins-- their weak subunit assemblies as demonstrated here by gel filtration at very dilute protein concentrations and their high oxygen affinities and reduced cooperativities reported previously by others but without a mechanistic basis. We demonstrate here that their high oxygen affinities are a consequence of their weak assemblies. Weak vs strong hemoglobin tetramers represent a regulatory mechanism to modulate oxygen binding capacity by altering the equilibrium between the various steps in the assembly process that can be described as an inverse allosteric effect. Copyright © 2016 Elsevier Inc. All rights reserved.
Thompson, S; Smith, M T
1985-11-01
It has been previously reported that the main diene-conjugated fatty acid in human plasma is a non-oxygen containing linoleic acid isomer (PL-9, 11-LA'). It has also been proposed that this isomer can be used as a specific marker of free radical-mediated lipid peroxidation in humans. Here we report that the in vitro induction of lipid peroxidation in human and rat blood with either UV irradiation or phenylhydrazine failed to increase the plasma levels of this isomer. The induction of lipid peroxidation in vivo in rats pretreated with either phenylhydrazine or bromotrichloromethane also failed to increase the plasma levels of this isomer. These findings demonstrate that PL-9, 11-LA' cannot be used as an in vivo marker of free radical-mediated lipid peroxidation in rats and casts doubts on its validity as a specific marker in humans.
Bernard, K. A.; Munro, C.; Wiebe, D.; Ongsansoy, E.
2002-01-01
Nineteen new Corynebacterium species or taxa described since 1995 have been associated with human disease. We report the characteristics of 72 strains identified as or most closely resembling 14 of these newer, medically relevant Corynebacterium species or taxa, as well as describe in brief an isolate of Corynebacterium bovis, a rare pathogen for humans. The bacteria studied in this report were nearly all derived from human clinical specimens and were identified by a polyphasic approach. Most were characterized by nearly full 16S rRNA gene sequence analysis. Some isolates were recovered from previously unreported sources and exhibited unusual phenotypes or represented the first isolates found outside Europe. Products of fermentation, with emphasis on the presence or absence of propionic acid, were also studied in order to provide an additional characteristic with which to differentiate among phenotypically similar species. PMID:12409436
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1992-01-01
During the past six months, we have continued work on the fronts of kinetic modeling of radioligands for studying neurotransmitter/receptor systems, iterative reconstruction techniques, and methodology for PET cerebral blood flow activation studies. Initial human PET studies have been performed and analyzed with many different kinetic model formulations to determine the quantitative potential of the neuronwsmitter/receptor ligand, ({sup 11}C)N-methyl piperidyl benzilate (NMPB), a muscarinic cholinergic antagonist. In addition, initial human studies using ({sup 11}C)tetrabenazine (TBZ), a marker for monoantine nerve terminal density. Results of the NWB studies have indicated that this new agent yields better estimates of receptor density thanmore » previous muscarinic ligands developed at our facility, ({sup 11}C)-TRB and ({sup 11}C)scopolamine. TRB and scopolamine have previously been shown to be only partially successful ligands due to sub-optimal values of the individual rate constants, causing varying degrees of flow limitation. This is found to be much less of a problem for NMPB due to the 2.0--2.5 fold increase in ligand transport observed in the human studies ({approximately}60% first pass extraction). A 2-parameter 2-compartment simplification had previously been implemented for the benzodiazepine ligand, (C-11)FMZ, and a similar model appears to be suitable for TBZ based on the preliminary human data.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1992-10-01
During the past six months, we have continued work on the fronts of kinetic modeling of radioligands for studying neurotransmitter/receptor systems, iterative reconstruction techniques, and methodology for PET cerebral blood flow activation studies. Initial human PET studies have been performed and analyzed with many different kinetic model formulations to determine the quantitative potential of the neuronwsmitter/receptor ligand, [{sup 11}C]N-methyl piperidyl benzilate (NMPB), a muscarinic cholinergic antagonist. In addition, initial human studies using [{sup 11}C]tetrabenazine (TBZ), a marker for monoantine nerve terminal density. Results of the NWB studies have indicated that this new agent yields better estimates of receptor density thanmore » previous muscarinic ligands developed at our facility, [{sup 11}C]-TRB and [{sup 11}C]scopolamine. TRB and scopolamine have previously been shown to be only partially successful ligands due to sub-optimal values of the individual rate constants, causing varying degrees of flow limitation. This is found to be much less of a problem for NMPB due to the 2.0--2.5 fold increase in ligand transport observed in the human studies ({approximately}60% first pass extraction). A 2-parameter 2-compartment simplification had previously been implemented for the benzodiazepine ligand, [C-11]FMZ, and a similar model appears to be suitable for TBZ based on the preliminary human data.« less
True Ulnar Artery Aneurysm in the Proximal Forearm: Case Report and Literature Review.
McHugh, Seamus Mark; Moloney, Michael Anthony; Greco, Elisa; Wheatcroft, Mark
2017-10-01
Ulnar artery aneurysms are rare with less than 150 previously reported. Previously ulnar aneurysms have been most commonly noted as occurring in the distal ulnar artery close to the palmar arch. We present the case of a 47-year-old male with a background history of human immunodeficiency virus (HIV) who attended our outpatient clinic with symptoms of distal embolization from a proximal ulnar artery aneurysm. Preoperatively, the aneurysm was thought to arise from the distal brachial artery, and only intraoperatively was the diagnosis of ulnar aneurysm made. The aneurysm was excised, and a reverse vein bypass graft anastomosed end to side on the brachial artery, and end to end on the distal ulnar. True ulnar artery aneurysms also involving the more proximal ulnar artery have been previously reported associated with vasculitic disorders. HIV has been previously associated with aneurysm formation in a number of anatomical locations. This case is noteworthy as it reports on the presentation and successful operative management of a true ulnar artery aneurysm arising in the proximal forearm in the setting of HIV, which has not been previously reported in medical literature. We present successful operative management of a true ulnar aneurysm in the proximal forearm using a reverse venous interposition bypass. Diagnosis of a proximal ulnar artery aneurysm may represent a diagnostic challenge given its rarity as it may mimic brachial artery aneurysm. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fields, C.A.
1994-09-01
This Report concludes the DOE Human Genome Program project, ``Identification of Genes in Anonymous DNA Sequence.`` The central goals of this project have been (1) understanding the problem of identifying genes in anonymous sequences, and (2) development of tools, primarily the automated identification system gm, for identifying genes. The activities supported under the previous award are summarized here to provide a single complete report on the activities supported as part of the project from its inception to its completion.
RADON REMOVAL BY POINT-OF-ENTRY GRANULAR ACTIVATED CARBON SYSTEMS: DESIGN PERFORMANCE AND COST
The report summarizes previous research conducted by Lowry Engineering, Inc. (LEI), the Maine Department of Human Services, Division of Health Engineering, and the University of Maine, Department of Civil Engineering, on the removal of Rn from drinking water supplies using granul...
ACTIVATED NEUTROPHILS INHIBIT PHAGOCYTOSIS BY HUMAN MONOCYTE CELLS IN VITRO
We have previously reported the correlation of decreased phagocytosis of opsonized zymosan by sputum monocytic cells with the increase in sputum neutrophils in volunteers 6h after inhalation of endotoxin (20,000 EU) (Alexis, et al. JACI, 2003;112:353). To define whether an intrin...
Nanodiamond particles (NDP) prepared by detonational processes have a number of industrial and analytical applications. Previous in vitro studies have reported NDP to be biologically inert with negligible cytotoxicity, implying that they are potentially suitable for biomedical ap...
A new worm infiltrating the human cornea: A report of 3 cases
USDA-ARS?s Scientific Manuscript database
Purpose: To characterize a new species of parasitic nematode that triggers uveitis. Observations: Three previously healthy, relatively young people each contracted a corneal stromal nematode that, upon surgical removal and examination of one of the worms, did not match any known nematodes. Clinical...
Development of a Multi-Sensor Cancer Detection Probe Final Report CRADA No. TC-2026-01
DOE Office of Scientific and Technical Information (OSTI.GOV)
Marion, J.; Hular, R.
This collaboration continued work started under a previous CRADA (TSB-2023-00) to take a detailed concept specification for a multi-sensor needle/probe suitable for breast cancer analysis and produce a prototype system suitable for human FDA trials.
ERIC Educational Resources Information Center
Goodman, Charles H.; Stone, Elizabeth W.
A study guide is presented for a course designed for the continuing education of professional librarians at the level of middle or upper management who find that they need understanding about human resources in the library system beyond that acquired on the job or in previous library education. The course has four units: (1) Management: A Systems…
Magnússon, S H; Guðmundsdóttir, S; Reynisson, E; Rúnarsson, A R; Harðardóttir, H; Gunnarson, E; Georgsson, F; Reiersen, J; Marteinsson, V Th
2011-10-01
Campylobacter jejuni isolates from various sources in Iceland were genotyped with the aim of assessing the genetic diversity, population structure, source distribution and campylobacter transmission routes to humans. A collection of 584 Campylobacter isolates were collected from clinical cases, food, animals and environment in Iceland in 1999-2002, during a period of national Campylobacter epidemic in Iceland. All isolates were characterized by pulse field gel electrophoresis (PFGE), and selected subset of 52 isolates representing the diversity of the identified PFGE types was further genotyped using multilocus sequence typing (MLST) and fla-SVR sequencing to gain better insight into the population structure. The results show a substantial diversity within the Icelandic Campylobacter population. Majority of the human Campylobacter infections originated from domestic chicken and cattle isolates. MLST showed the isolates to be distributed among previously reported and common sequence type complexes in the MLST database. The genotyping of Campylobacter from various sources has not previously been reported from Iceland, and the results of the study gave a valuable insight into the population structure of Camp. jejuni in Iceland, source distribution and transmission routes to humans. The geographical isolation of Iceland in the north Atlantic provides new information on Campylobacter population dynamics on a global scale. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology No claim to Icelandic Government works.
Can anaerobes be acid fast? A novel, clinically relevant acid fast anaerobe.
Navas, Maria E; Jump, Robin; Canaday, David H; Wnek, Maria D; SenGupta, Dhruba J; McQuiston, John R; Bell, Melissa
2016-08-01
Anaerobic acid fast bacilli (AFB) have not been previously reported in clinical microbiology. This is the second case report of a novel anaerobic AFB causing disease in humans. An anaerobic AFB was isolated from an abdominal wall abscess in a 64-year-old Caucasian diabetic male, who underwent distal pancreatectomy and splenectomy for resection of a pancreatic neuroendocrine tumour. The isolated bacteria were gram-variable and acid-fast, consisting of small irregular rods. The 16S rRNA gene sequence analysis showed that the isolate is a novel organism described in the literature only once before. The organism was studied at the CDC (Centers for Disease Control and Prevention) by the same group that worked with the isolates from the previous report; their findings suggest that the strain belongs to the suborder Corynebacterineae. This is the fifth reported case of an anaerobic AFB involved in clinical disease; its microbiological features and 16S RNA sequence are identical to previously reported cases. Clinical disease with this organism seems to be associated with recent history of surgery and abscess formation in deep soft tissues. Acquisition from surgical material is uncertain but seems unlikely.
Waste streams in a typical crewed space habitat: An update
NASA Technical Reports Server (NTRS)
Golub, M. A.; Wydeven, T.
1992-01-01
A compilation of generation rates and chemical compositions of potential waste streams in a typical crewed space habitat, reported in a prior NASA Technical Memorandum and a related journal article, was updated. This report augments that compilation by the inclusion of the following new data: those data uncovered since completion of the prior report; those obtained from Soviet literature relevant to life support issues; and those for various minor human body wastes not presented previously (saliva, flatus, hair, finger- and toenails, dried skin and skin secretions, tears, and semen), but included here for purposes of completeness. These waste streams complement those discussed previously: toilet waste (urine, feces, etc.), hygiene water (laundry, shower/handwash, dishwasher water and cleansing agents), trash, humidity condensate, perspiration and respiration water, trace contaminants, and dust generation. This report also reproduces the latest information on the environmental control and life support system design parameters for Space Station Freedom.
Peterson, Emily A; Boezio, Alessandro A; Andrews, Paul S; Boezio, Christiane M; Bush, Tammy L; Cheng, Alan C; Choquette, Deborah; Coats, James R; Colletti, Adria E; Copeland, Katrina W; DuPont, Michelle; Graceffa, Russell; Grubinska, Barbara; Kim, Joseph L; Lewis, Richard T; Liu, Jingzhou; Mullady, Erin L; Potashman, Michele H; Romero, Karina; Shaffer, Paul L; Stanton, Mary K; Stellwagen, John C; Teffera, Yohannes; Yi, Shuyan; Cai, Ti; La, Daniel S
2012-08-01
mTOR is a critical regulator of cellular signaling downstream of multiple growth factors. The mTOR/PI3K/AKT pathway is frequently mutated in human cancers and is thus an important oncology target. Herein we report the evolution of our program to discover ATP-competitive mTOR inhibitors that demonstrate improved pharmacokinetic properties and selectivity compared to our previous leads. Through targeted SAR and structure-guided design, new imidazopyridine and imidazopyridazine scaffolds were identified that demonstrated superior inhibition of mTOR in cellular assays, selectivity over the closely related PIKK family and improved in vivo clearance over our previously reported benzimidazole series. Copyright © 2012. Published by Elsevier Ltd.
Volaki, Konstantina; Pampanos, Andreas; Kitsiou-Tzeli, Sophia; Vrettou, Christina; Oikonomakis, Vasilis; Sofocleous, Christalena; Kanavakis, Emmanuel
2013-10-01
Molecular and neurobiological evidence for the involvement of neuroligins (particularly NLGN3 and NLGN4X genes) in autistic disorder is accumulating. However, previous mutation screening studies on these two genes have yielded controversial results. The present study explores, for the first time, the contribution of NLGN3 and NLGN4X genetic variants in Greek patients with autistic disorder. We analyzed the full exonic sequence of NLGN3 and NLGN4X genes in 40 patients strictly fulfilling the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria for autistic disorder. We identified nine nucleotide changes in NLGN4X--one probable causative mutation (p.K378R) previously reported by our research group, one novel variant (c.-206G>C), one nonvalidated single nucleotide polymorphism (SNP, rs111953947), and six known human SNPs reported in the SNP database--and one known human SNP in NLGN3 also reported in the SNP database. The variants identified are expected to be benign. However, they should be investigated in the context of variants in interacting cellular pathways to assess their contribution to the etiology of autism.
[Tetanus after cat scratch and bites in a previously immunized patient].
Fica, Alberto; Gaínza, Daniela; Ortigosa, Pablo
2017-04-01
Tetanus is declining due to vaccination, professional labor management and appropriate wound care. Tetanus cases have been reported despite immunization. We report the case of a previously healthy 21 years old female patient that presented a mild generalized tetanus requiring admission after mild and recurrent cat scratch and bites. She had received six vaccine shots during childhood, and a booster dose five years earlier after a rabbit bite. Symptoms appeared seven weeks after the last contact, and included headache, muscle spasms and mild opisthotonus. Laboratory evaluation, including CSF analysis and microbiological investigation, as well as imaging studies were all normal. The patient received 6,000 IU of human antitoxin immunoglobulin. No autonomic manifestations or respiratory compromise were registered. Symptoms resolved rapidly and she was discharge after seven days with an order to complete a tetanus toxoid immunization schedule with three doses. Tetanus is possible in urban settings with a declining epidemiologic curve of disease in previously immunized patients. Severity of disease is modulated by previous vaccination.
[Neuronal organization of thalamic nucleus reticularis in adult man].
Berezhnaia, L A
2005-01-01
The neuronal content of human thalamic nucleus reticularis was studied in serial sections cut in sagittal and frontal projections and impregnated with silver nitrate using Golgi method. The neuronal content of human thalamic nucleus reticularis was found to be more diverse than previously reported in animals and man. Besides two types of sparsely-branched long-dendritic spineless R1 and R2 neurons, this nucleus contained spiny cells. Medium and small-sized sparsely-branched short-dendritic neurons and densely-branched spiny cells were demonstrated. The principle of organization of human thalamic nucleus reticularis is described.
USDA-ARS?s Scientific Manuscript database
Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently proved for clinical trials. We have previously reported, for the first time, NDV Anhinga strain has an efficient cancer therapeutic efficacy in hepatoma. Tumor necrosis factor-related apo...
Investigating Mitochondrial Dysfunction in Human Lung Cells Exposed to Redox-Active PM Components
Exposure to ambient particulate matter (PM) causes cardiopulmonary morbidity and mortality through mechanisms that involve oxidative stress. 1,2-naphthoquinone (1,2-NQ) is a ubiquitous component of PM and a potent redox-active electrophile. We previously reported that 1,2-NQ incr...
Antibacterial properties of propolis (bee glue).
Grange, J M; Davey, R W
1990-01-01
Propolis (bee glue) was found to have antibacterial activity against a range of commonly encountered cocci and Gram-positive rods, including the human tubercle bacillus, but only limited activity against Gram-negative bacilli. These findings confirm previous reports of antimicrobial properties of this material, possibly attributable to its high flavonoid content. PMID:2182860
When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously believed. As a result of this, human health and environmental issues will be longer-lasting and more regionally variable...
Brain Systems for Assessing Facial Attractiveness
ERIC Educational Resources Information Center
Winston, Joel S.; O'Doherty, John; Kilner, James M.; Perrett, David I.; Dolan, Raymond J.
2007-01-01
Attractiveness is a facial attribute that shapes human affiliative behaviours. In a previous study we reported a linear response to facial attractiveness in orbitofrontal cortex (OFC), a region involved in reward processing. There are strong theoretical grounds for the hypothesis that coding stimulus reward value also involves the amygdala. The…
The Control of Human Aggression: An Incompatible Response Strategy.
ERIC Educational Resources Information Center
Baron, Robert A.
This is a brief report discussing ways of dealing with aggression in individuals. The author feels that previous approaches, such as catharsis or punishment, have proved inadequate, and that a more successful approach to reducing aggression involves the induction of incompatible reactions among aggressors. In the author's opinion, when angry…
Previous research has reported concurrent levels of pyrethroid insecticides and their environmental degradates in foods. These data raise concerns about using these same pyrethroid degradates found in the diet as urinary biomarkers of exposures in humans. The primary objective wa...
Endocarditis caused by Streptococcus canis: an emerging zoonosis?
Lacave, Guillaume; Coutard, Aymeric; Troché, Gilles; Augusto, Sandrine; Pons, Stéphanie; Zuber, Benjamin; Laurent, Virginie; Amara, Marlène; Couzon, Brigitte; Bédos, Jean-Pierre; Pangon, Béatrice; Grimaldi, David
2016-02-01
We report a human case of infective endocarditis caused by Streptococcus canis. Identification was carried out from positive blood culture using mass spectrometry and SodA gene sequencing. S. canis related zoonotic invasive infections may have been previously underdiagnosed due to inadequate identification of group G Streptococcus species.
Human babesiosis in Europe: what clinicians need to know.
Hildebrandt, A; Gray, J S; Hunfeld, K-P
2013-12-01
Although best known as an animal disease, human babesiosis is attracting increasing attention as a worldwide emerging zoonosis. Humans are commonly infected by the bite of ixodid ticks. Rare ways of transmission are transplacental, perinatal and transfusion-associated. Infection of the human host can cause a very severe host-mediated pathology including fever, and hemolysis leading to anemia, hyperbilirubinuria, hemoglobinuria and possible organ failure. In recent years, apparently owing to increased medical awareness and better diagnostic methods, the number of reported cases in humans is rising steadily worldwide. Hitherto unknown zoonotic Babesia spp. are now being reported from geographic areas where babesiosis was not previously known to occur and the growing numbers of travelers and immunocompromised individuals suggest that the frequency of cases in Europe will also continue to rise. Our review is intended to provide clinicians with practical information on the clinical management of this rare, but potentially life-threatening zoonotic disease. It covers epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the potential risk of transfusion-transmitted disease with a special focus on the European situation.
Occurrence of Putative Virulence Genes in Arcobacter Species Isolated from Humans and Animals
Douidah, Laid; de Zutter, Lieven; Baré, Julie; De Vos, Paul; Vandamme, Peter; Vandenberg, Olivier; Van den Abeele, Anne-Marie
2012-01-01
Interest in arcobacters in veterinary and human public health has increased since the first report of the isolation of arcobacters from food of animal origin. Since then, studies worldwide have reported the occurrence of arcobacters on food and in food production animals and have highlighted possible transmission, especially of Arcobacter butzleri, to the human population. In humans, arcobacters are associated with enteritis and septicemia. To assess their clinical relevance for humans and animals, evaluation of potential virulence factors is required. However, up to now, little has been known about the mechanisms of pathogenicity. Because of their close phylogenetic affiliation to the food-borne pathogen Campylobacter and their similar clinical manifestations, the presence of nine putative Campylobacter virulence genes (cadF, ciaB, cj1349, hecA, hecB, irgA, mviN, pldA, and tlyA) previously identified in the recent Arcobacter butzleri ATCC 49616 genome sequence was determined in a large set of human and animal Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii strains after the development of rapid and accurate PCR assays and confirmed by sequencing and dot blot hybridization. PMID:22170914
Age-Dependent Recombination Rates in Human Pedigrees
Hussin, Julie; Roy-Gagnon, Marie-Hélène; Gendron, Roxanne; Andelfinger, Gregor; Awadalla, Philip
2011-01-01
In humans, chromosome-number abnormalities have been associated with altered recombination and increased maternal age. Therefore, age-related effects on recombination are of major importance, especially in relation to the mechanisms involved in human trisomies. Here, we examine the relationship between maternal age and recombination rate in humans. We localized crossovers at high resolution by using over 600,000 markers genotyped in a panel of 69 French-Canadian pedigrees, revealing recombination events in 195 maternal meioses. Overall, we observed the general patterns of variation in fine-scale recombination rates previously reported in humans. However, we make the first observation of a significant decrease in recombination rates with advancing maternal age in humans, likely driven by chromosome-specific effects. The effect appears to be localized in the middle section of chromosomal arms and near subtelomeric regions. We postulate that, for some chromosomes, protection against non-disjunction provided by recombination becomes less efficient with advancing maternal age, which can be partly responsible for the higher rates of aneuploidy in older women. We propose a model that reconciles our findings with reported associations between maternal age and recombination in cases of trisomies. PMID:21912527
Rocky mountain spotted fever in the United States, 1997-2002.
Chapman, Alice S; Murphy, Staci M; Demma, Linda J; Holman, Robert C; Curns, Aaron T; McQuiston, Jennifer H; Krebs, John W; Swerdlow, David L
2006-10-01
The increased incidence of Rocky Mountain spotted fever (RMSF) in 1997-2002 compared with previous years may be related to enhanced awareness and reporting of RMSF as well as changes in human-vector interaction. However, reports on RMSF mortality underscore the need for physician vigilance in considering a diagnosis of RMSF for febrile individuals potentially exposed to ticks and stress the importance of treating such persons regardless of the presence of a rash.
Fusarium proliferatum as an agent of disseminated infection in an immunosuppressed patient.
Summerbell, R C; Richardson, S E; Kane, J
1988-01-01
Fusarium proliferatum was reported as the agent of a fatal disseminated infection in a child with lymphoblastic leukemia. The fungus has not been reported previously to cause disease in humans, but it is closely related to the known opportunistic pathogen F. verticillioides. It was distinguished by the production of clavate microconidia in chains from proliferating phialides. Resistance to amphotericin B and flucytosine in vitro was shown. Images PMID:3422646
An unusual osteomyelitis caused by Moraxella osloensis: A case report.
Alkhatib, Nidal J; Younis, Manaf H; Alobaidi, Ahmad S; Shaath, Nebal M
2017-01-01
Moraxella osloensis is a gram-negative coccobacillus, that is saprophytic on skin and mucosa, and rarely causing human infections. Reported cases of human infections usually occur in immunocompromised patients. We report the second case of M. osloensis-caused-osteomyelitis in literature, occurring in a young healthy man. The organism was identified by sequencing analysis of the 16S ribosomal RNA gene. Our patient was treated successfully with surgical debridement and intravenous third-generation cephalosporins. M. osloensis has been rarely reported to cause local or invasive infections. Our case report is the second case in literature and it is different from the previously reported case in that our patient has no chronic medical problems, no history of trauma, with unique presentation and features on the MRI and intraoperative finding. Proper diagnosis is essential for appropriate treatment of osteomyelitis. RNA gene sequence analysis is the primary method of M. osloensis diagnosis. M. osloensis is usually susceptible to simple antibiotics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.
Calin, George A; Liu, Chang-gong; Ferracin, Manuela; Hyslop, Terry; Spizzo, Riccardo; Sevignani, Cinzia; Fabbri, Muller; Cimmino, Amelia; Lee, Eun Joo; Wojcik, Sylwia E; Shimizu, Masayoshi; Tili, Esmerina; Rossi, Simona; Taccioli, Cristian; Pichiorri, Flavia; Liu, Xiuping; Zupo, Simona; Herlea, Vlad; Gramantieri, Laura; Lanza, Giovanni; Alder, Hansjuerg; Rassenti, Laura; Volinia, Stefano; Schmittgen, Thomas D; Kipps, Thomas J; Negrini, Massimo; Croce, Carlo M
2007-09-01
Noncoding RNA (ncRNA) transcripts are thought to be involved in human tumorigenesis. We report that a large fraction of genomic ultraconserved regions (UCRs) encode a particular set of ncRNAs whose expression is altered in human cancers. Genome-wide profiling revealed that UCRs have distinct signatures in human leukemias and carcinomas. UCRs are frequently located at fragile sites and genomic regions involved in cancers. We identified certain UCRs whose expression may be regulated by microRNAs abnormally expressed in human chronic lymphocytic leukemia, and we proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells. Our findings argue that ncRNAs and interaction between noncoding genes are involved in tumorigenesis to a greater extent than previously thought.
A new worm infiltrating the human cornea: A report of three cases.
McBurney-Lin, Shan; Khorram, David; Gee, Stephen; Hoberg, Eric P; Klassen-Fischer, Mary K; Neafie, Ronald C
2018-03-01
To characterize a new species of parasitic nematode that triggers uveitis. Three previously healthy, relatively young people each contracted a corneal stromal nematode that, upon surgical removal and examination, did not match any known nematodes. Clinical ocular findings included corneal opacification, visible corneal worms, conjunctival injection, and uveitis. The three cases presented here represent a previously undescribed parasitic infection of the cornea by an unidentified nematode. These findings may represent a previously unrecognized zoonotic infection from wildlife sources and potentially a newly documented nematode requiring description. Future clinical findings regarding this newly described nematode are needed to further develop our understanding of the disease.
Negi, Sanjay Singh; Gade, Neeta
2017-01-01
Pasteurella species are zoonotic bacterial pathogens implicated very infrequently in various human infections following animal bites or licks usually of dogs and cats. This case report described a rare clinical presentation of dacryocystitis caused by P.canis in a Human Immunodeficiency Virus (HIV) positive young male patient involved in caring of cattle. It advocates the utmost need of recognizing the wide clinical manifestation spectrum of P.canis even without prior penetrating injury. P.canis associated clinical infection is more extensive than had been thought previously especially in immunocompromised patient. Early accurate identification and evidence based anti-microbial therapy may prove crucial in preventing further potential complications. PMID:28384864
Shen, Yinzhong; Lu, Hongzhou
2017-03-22
Since the first outbreak of human infection with avian influenza A (H7N9) virus was identified in 2013, five seasonal outbreaks have occurred in China. The fifth outbreak started earlier than usual. A sudden increase in cases of human infection with avian influenza A (H7N9) virus has been reported in China since September 2016, and the number of cases reported in this season is exceeding that reported in previous seasons. This increase in the number of new cases of H7N9 infection has caused domestic and international concern. This paper summarizes the current prevalence of H7N9 in China and it also discusses measures that China has taken to control this outbreak. This paper also describes steps China must take in the future. This paper can serve as a reference for prevention and control of H7N9 outbreaks around the world.
Smoking, haptoglobin and fertility in humans
Bottini, N; Magrini, A; MacMurray, J; Cosmi, E; Nicotra, M; Gloria-Bottini, F; Bergamaschi, A
2003-01-01
A prospective study on two samples of consecutive puerperae (total n° 667) from two populations has been carried out in order to investigate the possible effect of smoking habit on relationship between fertility and haptoglobin phenotype. In both populations the negative association previously reported between age of pueperae and Haptoglobin *1/*1 phenotype is present only in women with smoking habit pointing to an interaction between Hp and smoke on human fertility. This suggests that the effects of smoke on fertility are dependent on the Hp phenotype.
ERIC Educational Resources Information Center
Goodman, Charles H.; Stone, Elizabeth W.
A leader's handbook is presented for a course designed for the continuing education of professional librarians at the level of middle or upper management who find that they need understanding about human resources in the library system beyond that acquired on the job or in previous library education. The course has four units: (1) Management: A…
Montagnani, Carlotta; Pecile, Patrizia; Moriondo, Maria; Petricci, Patrizia; Becciani, Sabrina; Chiappini, Elena; Indolfi, Giuseppe; Rossolini, Gian Maria; Azzari, Chiara; de Martino, Maurizio; Galli, Luisa
2015-06-01
We report the first human case of meningitis and sepsis caused in a child by Actinobacillus suis or A. equuli, a common opportunistic pathogen of swine or horses, respectively. Identification was performed by matrix-assisted laser desorption ionization-time of flight mass spectrometry and real-time PCR assay. A previous visit to a farm was suspected as the source of infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
1978-01-01
The assertion that ingestion of human erythrocytes is restricted to invasive strains of Entamoeba histolytica has not been evaluated previously by comparative studies. In this report we describe the in vitro ingestion of human erythrocytes by pathogenic and nonpathogenic Entamoeba. Microscopic evaluation of erythrophagocytosis by eight different Entamoeba grown in culture revealed that strains of E. histolytica isolated from cases of human dysentery show a much higher rate of erythrocyte ingestion than nonpathogenic strains. However, all strains are able to phagocytize erythrocytes. The extremely high rate of phagocytic activity shown by pathogenic E. histolytica could be one of the properties related to the pathogenicity of this parasitic protozoan. PMID:722237
Hirata, M; Tsuchida, A; Iwao, T; Sasaki, T; Matsubara, K; Yamamoto, S; Morinaka, K; Kawasaki, Y; Fujimoto, Y; Inoue, H; Kariya, K; Kajiyama, G
1999-06-01
We have previously reported that cholecystokinin (CCK) plays an important role in the invasiveness and the production of matrix metalloproteinase-9 (MMP-9) in two human pancreatic cancer cell lines. In this study we investigated the pathway of the invasiveness associated with MMP-9 of those lines regulated by CCK. Two human pancreatic cancer cell lines were treated with CCK-8 alone, CCK-8 and staurosporine, or CCK-8 and indomethacine. The invasiveness and the production of MMP-9 were decreased with staurosporine but not indomethacine. These results suggest that CCK may regulate the invasiveness and the production of MMP-9 via protein kinase C in human pancreatic cancer cell lines.
Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast
Mexia, Nikitia; Gaitanis, George; Velegraki, Aristea; Soshilov, Anatoly; Denison, Michael S.; Magiatis, Prokopios
2015-01-01
Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in human skin and are highly potent activators of the aryl hydrocarbon receptor (AhR) and AhR-dependent gene expression. Chemical analysis of an EtOAc extract of a M. furfur strain obtained from diseased human skin and grown on L-tryptophan agar revealed several known AhR active tryptophan metabolites along with a previously unidentified compound, pityriazepin. While its structure resembled that of the known alkaloid pityriacitrin, the comprised pyridine ring had been transformed into an azepinone. The indoloazepinone scaffold of pityriazepin is extremely rare in nature and has only been reported once previously. Pityriazepin, like the other isolated compounds, was found to be a potent activator of the AhR-dependent reporter gene assays in recombinant cell lines derived from four different species, although significant species differences in relative potency was observed. The ability of pityriazepin to competitively bind to the AhR and directly stimulate AhR DNA binding classified it as a new naturally-occurring potent AhR agonist. Malassezia furfur produces an expanded collection of extremely potent naturally occurring AhR agonists, which produce their biological effects in a species-specific manner.1 PMID:25721496
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martha, A.; Ferrel, R.E.; Hittner, H.M.
1994-09-01
Aniridia (iris hyplasia) is a autosomal dominant congenital disorder of the eye. Mutations in the human aniridia (PAX6) gene have now been identified in many patients from various ethnic groups. In the present study we describe new mutations in this gene. Out of four mutations found, three were novel mutations; the fourth one is identical to the previously reported mutations (C{yields}T transition at nt 240). The three novel mutations analyzed were in the glycine-rich region (two) and in the proline/serine/threonine-rich (PST) region (one). Previously no mutations were reported for the glycine-rich region in humans. One of the mutations found inmore » this region is associated with cataracts in an aniridia family. The other splice mutation found in the PST domain is associated with anosmia (lack of sensation to smell) in a sporadic aniridia case. Two of the mutations presented here, one in the glycine-rich region and the other in the PST domain, were not detected by SSCR. These mutations could be detected by using MDE gel and heteroduplex information. All mutations found in the present study are similar in that 32 of 33 PAX6 mutations result in protein truncation and haploinsufficiency.« less
Contact variables for exposure to avian influenza H5N1 virus at the human-animal interface.
Rabinowitz, P; Perdue, M; Mumford, E
2010-06-01
Although the highly pathogenic avian influenza H5N1 virus continues to cause infections in both avian and human populations, the specific zoonotic risk factors remain poorly understood. This review summarizes available evidence regarding types of contact associated with transmission of H5N1 virus at the human-animal interface. A systematic search of the published literature revealed five analytical studies and 15 case reports describing avian influenza transmission from animals to humans for further review. Risk factors identified in analytical studies were compared, and World Health Organization-confirmed cases, identified in case reports, were classified according to type of contact reported using a standardized algorithm. Although cases were primarily associated with direct contact with sick/unexpectedly dead birds, some cases reported only indirect contact with birds or contaminated environments or contact with apparently healthy birds. Specific types of contacts or activities leading to exposure could not be determined from data available in the publications reviewed. These results support previous reports that direct contact with sick birds is not the only means of human exposure to avian influenza H5N1 virus. To target public health measures and disease awareness messaging for reducing the risk of zoonotic infection with avian influenza H5N1 virus, the specific types of contacts and activities leading to transmission need to be further understood. The role of environmental virus persistence, shedding of virus by asymptomatic poultry and disease pathophysiology in different avian species relative to human zoonotic risk, as well as specific modes of zoonotic transmission, should be determined.
Singh, Satyakam; Prasad, Nagarajan Rajendra; Kapoor, Khyati; Chufan, Eduardo E.; Patel, Bhargav A.; Ambudkar, Suresh V.; Talele, Tanaji T.
2014-01-01
Multidrug resistance (MDR) caused by ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp) through extrusion of anticancer drugs from the cells is a major cause of failure to cancer chemotherapy. Previously, selenazole containing cyclic peptides were reported as P-gp inhibitors and these were also used for co-crystallization with mouse P-gp, which has 87% homology to human P-gp. It has been reported that human P-gp, can simultaneously accommodate 2-3 moderate size molecules at the drug binding pocket. Our in-silico analysis based on the homology model of human P-gp spurred our efforts to investigate the optimal size of (S)-valine-derived thiazole units that can be accommodated at drug-binding pocket. Towards this goal, we synthesized varying lengths of linear and cyclic derivatives of (S)-valine-derived thiazole units to investigate the optimal size, lipophilicity and the structural form (linear and cyclic) of valine-derived thiazole peptides that can accommodate well in the P-gp binding pocket and affects its activity, previously an unexplored concept. Among these oligomers, lipophilic linear- (13) and cyclic-trimer (17) derivatives of QZ59S-SSS were found to be the most and equally potent inhibitors of human P-gp (IC50 = 1.5 μM). Cyclic trimer and linear trimer being equipotent, future studies can be focused on non-cyclic counterparts of cyclic peptides maintaining linear trimer length. Binding model of the linear trimer (13) within the drug-binding site on the homology model of human P-gp represents an opportunity for future optimization, specifically replacing valine and thiazole groups in the non-cyclic form. PMID:24288265
Singh, Satyakam; Prasad, Nagarajan Rajendra; Kapoor, Khyati; Chufan, Eduardo E; Patel, Bhargav A; Ambudkar, Suresh V; Talele, Tanaji T
2014-01-03
Multidrug resistance caused by ATP binding cassette transporter P-glycoprotein (P-gp) through extrusion of anticancer drugs from the cells is a major cause of failure in cancer chemotherapy. Previously, selenazole-containing cyclic peptides were reported as P-gp inhibitors and were also used for co-crystallization with mouse P-gp, which has 87 % homology to human P-gp. It has been reported that human P-gp can simultaneously accommodate two to three moderately sized molecules at the drug binding pocket. Our in silico analysis, based on the homology model of human P-gp, spurred our efforts to investigate the optimal size of (S)-valine-derived thiazole units that can be accommodated at the drug binding pocket. Towards this goal, we synthesized varying lengths of linear and cyclic derivatives of (S)-valine-derived thiazole units to investigate the optimal size, lipophilicity, and structural form (linear or cyclic) of valine-derived thiazole peptides that can be accommodated in the P-gp binding pocket and affects its activity, previously an unexplored concept. Among these oligomers, lipophilic linear (13) and cyclic trimer (17) derivatives of QZ59S-SSS were found to be the most and equally potent inhibitors of human P-gp (IC50 =1.5 μM). As the cyclic trimer and linear trimer compounds are equipotent, future studies should focus on noncyclic counterparts of cyclic peptides maintaining linear trimer length. A binding model of the linear trimer 13 within the drug binding site on the homology model of human P-gp represents an opportunity for future optimization, specifically replacing valine and thiazole groups in the noncyclic form. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Toda, Mitsunori; Kawamoto, Teruya; Ueha, Takeshi; Kishimoto, Kenta; Hara, Hitomi; Fukase, Naomasa; Onishi, Yasuo; Harada, Risa; Minoda, Masaya; Kurosaka, Masahiro; Akisue, Toshihiro
2013-09-01
Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a 'decoy' for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has 'non-decoy' functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.
Evidence of infection with H4 and H11 avian influenza viruses among Lebanese chicken growers.
Kayali, Ghazi; Barbour, Elie; Dbaibo, Ghassan; Tabet, Carelle; Saade, Maya; Shaib, Houssam A; Debeauchamp, Jennifer; Webby, Richard J
2011-01-01
Human infections with H5, H7, and H9 avian influenza viruses are well documented. Exposure to poultry is the most important risk factor for humans becoming infected with these viruses. Data on human infection with other low pathogenicity avian influenza viruses is sparse but suggests that such infections may occur. Lebanon is a Mediterranean country lying under two major migratory birds flyways and is home to many wild and domestic bird species. Previous reports from this country demonstrated that low pathogenicity avian influenza viruses are in circulation but highly pathogenic H5N1 viruses were not reported. In order to study the extent of human infection with avian influenza viruses in Lebanon, we carried out a seroprevalence cross-sectional study into which 200 poultry-exposed individuals and 50 non-exposed controls were enrolled. We obtained their sera and tested it for the presence of antibodies against avian influenza viruses types H4 through H16 and used a questionnaire to collect exposure data. Our microneutralization assay results suggested that backyard poultry growers may have been previously infected with H4 and H11 avian influenza viruses. We confirmed these results by using a horse red blood cells hemagglutination inhibition assay. Our data also showed that farmers with antibodies against each virus type clustered in a small geographic area suggesting that unrecognized outbreaks among birds may have led to these human infections. In conclusion, this study suggests that occupational exposure to chicken is a risk factor for infection with avian influenza especially among backyard growers and that H4 and H11 influenza viruses may possess the ability to cross the species barrier to infect humans.
Buckmaster, Paul S.; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M. D.; Van Bonn, William
2014-01-01
California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and the pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin-immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy. PMID:24638960
Kolata, Stefan; Light, Kenneth; Matzel, Louis D.
2008-01-01
It has been established that both domain-specific (e.g. spatial) as well as domain-general (general intelligence) factors influence human cognition. However, the separation of these processes has rarely been attempted in studies using laboratory animals. Previously, we have found that the performances of outbred mice across a wide range of learning tasks correlate in such a way that a single factor can explain 30– 44% of the variance between animals. This general learning factor is in some ways qualitatively and quantitatively analogous to general intelligence in humans. The complete structure of cognition in mice, however, has not been explored due to the limited sample sizes of our previous analyses. Here we report a combined analysis from 241 CD-1 mice tested in five primary learning tasks, and a subset of mice tested in two additional learning tasks. At least two (possibly three) of the seven learning tasks placed explicit demands on spatial and/or hippocampus-dependent processing abilities. Consistent with previous findings, we report a robust general factor influencing learning in mice that accounted for 38% of the variance across tasks. In addition, a domain-specific factor was found to account for performance on that subset of tasks that shared a dependence on hippocampal and/or spatial processing. These results provide further evidence for a general learning/cognitive factor in genetically heterogeneous mice. Furthermore (and similar to human cognitive performance), these results suggest a hierarchical structure to cognitive processes in this genetically heterogeneous species. PMID:19129932
Jackson, Robert S.; Creemers, John W.M.; Farooqi, I. Sadaf; Raffin-Sanson, Marie-Laure; Varro, Andrea; Dockray, Graham J.; Holst, Jens J.; Brubaker, Patricia L.; Corvol, Pierre; Polonsky, Kenneth S.; Ostrega, Diane; Becker, Kenneth L.; Bertagna, Xavier; Hutton, John C.; White, Anne; Dattani, Mehul T.; Hussain, Khalid; Middleton, Stephen J.; Nicole, Thomasina M.; Milla, Peter J.; Lindley, Keith J.; O’Rahilly, Stephen
2003-01-01
We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the clinical presentation of Subject B was dominated by severe refractory neonatal diarrhea, malabsorptive in type. Subsequent investigation of Subject A revealed marked small-intestinal absorptive dysfunction, which was not previously clinically suspected. We postulate that PC1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A’s negligible PC1 activity, some mature ACTH and glucagon-like peptide 17-36amide were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species. PMID:14617756
REVISITING GLYCOGEN CONTENT IN THE HUMAN BRAIN
Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R.
2015-01-01
Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3–4 µmol/g brain glycogen content using in vivo 13C magnetic resonance spectroscopy (MRS) in conjunction with [1-13C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3–5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state 13C labeling in glycogen, here we administered [1-13C]glucose to healthy volunteers for 80 hours. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-13C]glucose administration and 13C-glycogen levels in the occipital lobe were measured by 13C MRS approximately every 12 hours. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the 13C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain. PMID:26202425
Revisiting Glycogen Content in the Human Brain.
Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R
2015-12-01
Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.
West Nile virus activity--United States, 2006.
2007-06-08
West Nile virus (WNV) is the leading cause of arboviral encephalitis in the United States. Originally discovered in Africa in 1937, WNV was first detected in the western hemisphere in 1999 in New York City. Since then, WNV has caused seasonal epidemics of febrile illness and severe neurologic disease in the United States. This report summarizes provisional WNV surveillance data for 2006 reported to CDC as of April 3, 2007. During 2006, WNV transmission to humans or animals expanded into 52 counties that had not previously reported transmission and recurred in 1,350 counties where transmission had been reported in previous years. In addition, 1,491 cases of WNV neuroinvasive disease (WNND) were reported in the United States during this period, amounting to a 14% increase from 2005 and the largest number reported since 2003. On the basis of extrapolations from past serosurveys, an estimated 41,750 cases of non-neuroinvasive WNV disease occurred in 2006; of these cases, 2,770 were reported. These findings highlight the need for ongoing surveillance, mosquito control, promotion of personal protection from mosquito bites, and research into additional prevention strategies.
Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees.
Chabot, Adrien; Shrit, Ralla A; Blekhman, Ran; Gilad, Yoav
2007-08-01
Most phenotypic differences between human and chimpanzee are likely to result from differences in gene regulation, rather than changes to protein-coding regions. To date, however, only a handful of human-chimpanzee nucleotide differences leading to changes in gene regulation have been identified. To hone in on differences in regulatory elements between human and chimpanzee, we focused on 10 genes that were previously found to be differentially expressed between the two species. We then designed reporter gene assays for the putative human and chimpanzee promoters of the 10 genes. Of seven promoters that we found to be active in human liver cell lines, human and chimpanzee promoters had significantly different activity in four cases, three of which recapitulated the gene expression difference seen in the microarray experiment. For these three genes, we were therefore able to demonstrate that a change in cis influences expression differences between humans and chimpanzees. Moreover, using site-directed mutagenesis on one construct, the promoter for the DDA3 gene, we were able to identify three nucleotides that together lead to a cis regulatory difference between the species. High-throughput application of this approach can provide a map of regulatory element differences between humans and our close evolutionary relatives.
Mas-Coma, S; Bargues, M D; Valero, M A
2014-12-01
Before the 1990s, human fascioliasis diagnosis focused on individual patients in hospitals or health centres. Case reports were mainly from developed countries and usually concerned isolated human infection in animal endemic areas. From the mid-1990s onwards, due to the progressive description of human endemic areas and human infection reports in developing countries, but also new knowledge on clinical manifestations and pathology, new situations, hitherto neglected, entered in the global scenario. Human fascioliasis has proved to be pronouncedly more heterogeneous than previously thought, including different transmission patterns and epidemiological situations. Stool and blood techniques, the main tools for diagnosis in humans, have been improved for both patient and survey diagnosis. Present availabilities for human diagnosis are reviewed focusing on advantages and weaknesses, sample management, egg differentiation, qualitative and quantitative diagnosis, antibody and antigen detection, post-treatment monitoring and post-control surveillance. Main conclusions refer to the pronounced difficulties of diagnosing fascioliasis in humans given the different infection phases and parasite migration capacities, clinical heterogeneity, immunological complexity, different epidemiological situations and transmission patterns, the lack of a diagnostic technique covering all needs and situations, and the advisability for a combined use of different techniques, at least including a stool technique and a blood technique.
Previous studies have revealed that hair trace element concentrations can reflect exposure in cases of frank poisoning and deficiency. Correlations have been found also in some populations living in regions where metallurgic processes are conducted. This study reports significant...
DOT National Transportation Integrated Search
2003-01-01
This final report describes a follow-on study to the previous Crash Avoidance Metrics Partnership (CAMP) human factors work addressing Forward Collision Warning (FCW) timing requirements. This research extends this work by gathering not only "last-se...
DOE Scientists Contribute to 2007 Nobel Peace Prize Research about Climate
and resources were devoted to modeling the interactive effects of consequences, that is to say effects are more immediate and profound than previously anticipated, and old questions (are humans the Lawrence Livermore National Laboratory, DOE Technical Report, May 2005 Climate Effects of Global Land Cover
A Descriptive Analysis of Students Seeking HIV Antibody Testing at a University Health Service.
ERIC Educational Resources Information Center
Anastasi, Marie-Christine; Sawyer, Robin G.; Pinciaro, Paul J.
1999-01-01
Investigated characteristics of students voluntarily seeking human immunodeficiency virus (HIV) antibody testing at a university health center. Data from student surveys indicated that: 59% were women; reported rates of unintended pregnancy and sexually transmitted diseases were low; nearly one-third had had previous HIV testing; 40% reported…
The study of human venous system dynamics using hybrid computer modeling
NASA Technical Reports Server (NTRS)
Snyder, M. F.; Rideout, V. C.
1972-01-01
A computer-based model of the cardiovascular system was created emphasizing effects on the systemic venous system. Certain physiological aspects were emphasized: effects of heart rate, tilting, changes in respiration, and leg muscular contractions. The results from the model showed close correlation with findings previously reported in the literature.
Triclosan (TCS), a broad-spectrum antimicrobial agent found in many personal care products, has been detected in humans and has been shown to interact with endocrine systems in rats. We previously reported that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on u...
DOT National Transportation Integrated Search
1980-03-01
This report presents the findings of a workshop on the chemical analysis of human body fluids for drugs of interest in highway safety. A cross-disciplinary panel of experts reviewed the list of drugs of interest developed in a previous workshop and d...
USDA-ARS?s Scientific Manuscript database
Our previous report showed that concomitant supplementation of lycopene and eicosa-pentaenoic acid synergistically inhibited the proliferation of human colon cancer HT-29 cells in vitro. To validate our findings, the present study investigated whether consumption of lycopene and fish oil would help ...
Weyrich, Andrew S.; Denis, Melvin M.; Schwertz, Hansjorg; Tolley, Neal D.; Foulks, Jason; Spencer, Eliott; Kraiss, Larry W.; Albertine, Kurt H.; McIntyre, Thomas M.
2007-01-01
New activities of human platelets continue to emerge. One unexpected response is new synthesis of proteins from previously transcribed RNAs in response to activating signals. We previously reported that activated human platelets synthesize B-cell lymphoma-3 (Bcl-3) under translational control by mammalian target of rapamycin (mTOR). Characterization of the ontogeny and distribution of the mTOR signaling pathway in CD34+ stem cell–derived megakaryocytes now demonstrates that they transfer this regulatory system to developing proplatelets. We also found that Bcl-3 is required for condensation of fibrin by activated platelets, demonstrating functional significance for mTOR-regulated synthesis of the protein. Inhibition of mTOR by rapamycin blocks clot retraction by human platelets. Platelets from wild-type mice synthesize Bcl-3 in response to activation, as do human platelets, and platelets from mice with targeted deletion of Bcl-3 have defective retraction of fibrin in platelet-fibrin clots mimicking treatment of human platelets with rapamycin. In contrast, overexpression of Bcl-3 in a surrogate cell line enhanced clot retraction. These studies identify new features of post-transcriptional gene regulation and signal-dependant protein synthesis in activated platelets that may contribute to thrombus and wound remodeling and suggest that posttranscriptional pathways are targets for molecular intervention in thrombotic disorders. PMID:17110454
Kim, Kun-Yong; Hysolli, Eriona; Tanaka, Yoshiaki; Wang, Brandon; Jung, Yong-Wook; Pan, Xinghua; Weissman, Sherman Morton; Park, In-Hyun
2014-06-03
Induced pluripotent stem cells (iPSCs) acquire embryonic stem cell (ESC)-like epigenetic states, including the X chromosome. Previous studies reported that human iPSCs retain the inactive X chromosome of parental cells, or acquire two active X chromosomes through reprogramming. Most studies investigated the X chromosome states in established human iPSC clones after completion of reprogramming. Thus, it is still not fully understood when and how the X chromosome reactivation occurs during reprogramming. Here, we report a dynamic change in the X chromosome state throughout reprogramming, with an initial robust reactivation of the inactive X chromosome followed by an inactivation upon generation of nascent iPSC clones. iPSCs with two active X chromosomes or an eroded X chromosome arise in passaging iPSCs. These data provide important insights into the plasticity of the X chromosome of human female iPSCs and will be crucial for the future application of such cells in cell therapy and X-linked disease modeling.
What Is Trophoblast? A Combination of Criteria Define Human First-Trimester Trophoblast
Lee, Cheryl Q.E.; Gardner, Lucy; Turco, Margherita; Zhao, Nancy; Murray, Matthew J.; Coleman, Nicholas; Rossant, Janet; Hemberger, Myriam; Moffett, Ashley
2016-01-01
Summary Controversy surrounds reports describing the derivation of human trophoblast cells from placentas and embryonic stem cells (ESC), partly due to the difficulty in identifying markers that define cells as belonging to the trophoblast lineage. We have selected criteria that are characteristic of primary first-trimester trophoblast: a set of protein markers, HLA class I profile, methylation of ELF5, and expression of microRNAs (miRNAs) from the chromosome 19 miRNA cluster (C19MC). We tested these criteria on cells previously reported to show some phenotypic characteristics of trophoblast: bone morphogenetic protein (BMP)-treated human ESC and 2102Ep, an embryonal carcinoma cell line. Both cell types only show some, but not all, of the four trophoblast criteria. Thus, BMP-treated human ESC have not fully differentiated to trophoblast. Our study identifies a robust panel, including both protein and non-protein-coding markers that, in combination, can be used to reliably define cells as characteristic of early trophoblast. PMID:26862703
Pinsk, Mark A; Arcaro, Michael; Weiner, Kevin S; Kalkus, Jan F; Inati, Souheil J; Gross, Charles G; Kastner, Sabine
2009-05-01
Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas.
Neural Representations of Faces and Body Parts in Macaque and Human Cortex: A Comparative fMRI Study
Pinsk, Mark A.; Arcaro, Michael; Weiner, Kevin S.; Kalkus, Jan F.; Inati, Souheil J.; Gross, Charles G.; Kastner, Sabine
2009-01-01
Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part–selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part–selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas. PMID:19225169
New Monoclonal Antibodies to Defined Cell Surface Proteins on Human Pluripotent Stem Cells.
O'Brien, Carmel M; Chy, Hun S; Zhou, Qi; Blumenfeld, Shiri; Lambshead, Jack W; Liu, Xiaodong; Kie, Joshua; Capaldo, Bianca D; Chung, Tung-Liang; Adams, Timothy E; Phan, Tram; Bentley, John D; McKinstry, William J; Oliva, Karen; McMurrick, Paul J; Wang, Yu-Chieh; Rossello, Fernando J; Lindeman, Geoffrey J; Chen, Di; Jarde, Thierry; Clark, Amander T; Abud, Helen E; Visvader, Jane E; Nefzger, Christian M; Polo, Jose M; Loring, Jeanne F; Laslett, Andrew L
2017-03-01
The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types. Stem Cells 2017;35:626-640. © 2016 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
Distinct human antibody response to the biological warfare agent Burkholderia mallei
Varga, John J.; Vigil, Adam; DeShazer, David; Waag, David M.; Felgner, Philip; Goldberg, Joanna B.
2012-01-01
The genetic similarity between Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. In 2000, the first human case of glanders in North America since 1945 was reported in a microbiology laboratory worker. Leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohort of melioidosis patients in southeast Asia, we describe the antibody response in a human with glanders. Analysis of 156 peptides present on the array revealed antibodies against 17 peptides with a > 2-fold increase in this infection. Unexpectedly, when the glanders data were compared with a previous data set from B. pseudomallei infections, there were only two highly increased antibodies shared between these two infections. These findings have implications in the diagnosis and treatment of B. mallei and B. pseudomallei infections. PMID:23076276
The Orion Atmosphere Revitalization Technology in Manned Ambient Pressure Space Suit Testing
NASA Technical Reports Server (NTRS)
Button, Amy; Sweterlitsch, Jeffrey
2011-01-01
An amine-based carbon dioxide (CO2) and water vapor sorbent in pressure-swing regenerable beds has been developed by Hamilton Sundstrand and baselined for the Atmosphere Revitalization System (ARS) for moderate duration missions of the Orion Multipurpose Crew Vehicle. The Orion ARS is designed to support not only open-cabin operations, tests of which have been reported in previous years at this conference, but also closed space suit-loop operations. A previous low-pressure suit loop test was performed with a human metabolic simulator, and humans wearing emergency masks were tested in a closed-loop configuration before that. In late 2011, simple tests were performed in a suit-loop configuration with human test subjects in prototype space suits with prototype umbilicals at ambient and two slightly above-ambient pressures. Trace contaminant filters and a prototype blower were also incorporated into the test rig. This paper discusses the performance of the ARS technology in that 2011 test configuration.
Left-right axis asymmetry determining human Cryptic gene is transcriptionally repressed by Snail.
Gupta, Kartik; Pilli, Vijaya Satish Sekhar; Aradhyam, Gopala Krishna
2016-10-28
Establishment of the left-right axis is important for positioning organs asymmetrically in the developing vertebrate-embryo. A number of factors like maternally deposited molecules have emerged essential in initiating the specification of the axis; the downstream events, however, are regulated by signal-transduction and gene-expression changes identifying which remains a crucial challenge. The EGF-CFC family member Cryptic, that functions as a co-receptor for some TGF-beta ligands, is developmentally expressed in higher mammals and mutations in the gene cause loss or change in left-right axis asymmetry. Despite the strong phenotype, no transcriptional-regulator of this gene is known till date. Using promoter-analyses tools, we found strong evidence that the developmentally essential transcription factor Snail binds to the human Cryptic-promoter. We cloned the promoter-region of human Cryptic in a reporter gene and observed decreased Cryptic-promoter activation upon increasing Snail expression. Further, the expression of Cryptic is down-regulated upon exogenous Snail expression, validating the reporter assays and the previously identified role of Snail as a transcriptional repressor. Finally, we demonstrate using gel-shift assay that Snail in nuclear extract of PANC1 cells interacts with the promoter-construct bearing putative Snail binding sites and confirm this finding using chromatin immunoprecipitation assay. Snail represses the expression of human Cryptic and therefore, might affect the signaling via Nodal that has previously been demonstrated to specify the left-right axis using the EGF-CFC co-receptors.
High lipid storage in vacoular forms of subtype 6 Blastocystis sp. in ostrich.
Chandrasekaran, Hemalatha; Govind, Suresh Kumar; Panchadcharam, Chandrawathani; Bathmanaban, Premaalatha; Raman, Kalyani; Thergarajan, Gaythri
2014-10-30
Blastocystis sp., a widely prevalent intestinal protozoan parasite is found in a wide range of animals, including humans. The possibility of zoonotic transmission to human from birds especially ostriches led us to investigate on the cross infectivity of Blastocystis sp. isolated from the ostrich feces as well as the phenotypic and subtype characteristics. There is a need to investigate this especially with the rising number of ostrich farms due to the growing global ostrich industry. 100% of the ostriches were found to be positive for Blastocystis sp. using the in-vitro cultivation method. Transmission electron microscopy revealed high electron dense material in the central body of the vacoular forms. The membrane layer of the ostrich isolate was significantly (p = 0.003) thicker as compared to human isolate. Sudan staining revealed that this was lipid accumulation. We provide evidence for the first time, the existence of subtype 6 which has been previously reported only in pigs and cattle. Cysts, ranging from 3.0 to 7.0 μm in diameter caused experimental infection in Sprague Dawley rats implicating that Blastocystis sp. isolated from ostriches exhibits low host specificity. The study for the first time demonstrates that Blastocystis sp. subtype 6 do exist in ostriches and show high lipid storage in the vacuoles of the parasites. The study further provides evidence for potential zoonotic transmission in ostrich farms as Blastocystis subtype 6 can infect rats and the same subtype have been previously reported in humans.
Recombinant cathepsin E has no proteolytic activity at neutral pH.
Zaidi, Nousheen; Herrmann, Timo; Voelter, Wolfgang; Kalbacher, Hubert
2007-08-17
Cathepsin E (CatE) is a major intracellular aspartic protease reported to be involved in cellular protein degradation and several pathological processes. Distinct cleavage specificities of CatE at neutral and acidic pH have been reported previously in studies using CatE purified from human gastric mucosa. Here, in contrast, we have analyzed the proteolytic activity of recombinant CatE at acidic and neutral pH using two separate approaches, RP-HPLC and FRET-based proteinase assays. Our data clearly indicate that recombinant CatE does not possess any proteolytic activity at all at neutral pH and was unable to cleave the peptides glucagon, neurotensin, and dynorphin A that were previously reported to be cleaved by CatE at neutral pH. Even in the presence of ATP, which is known to stabilize CatE, no proteolytic activity was observed. These discrepant results might be due to some contaminating factor present in the enzyme preparations used in previous studies or may reflect differences between recombinant CatE and the native enzyme.
Chen, S C; You, S H; Liu, C Y; Chio, C P; Liao, C M
2012-09-01
The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 10(3)-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection.
NASA Astrophysics Data System (ADS)
Juday, Richard D.; Loshin, David S.
1989-06-01
We are investigating image coordinate transformations possibly to be used in a low vision aid for human patients. These patients typically have field defects with localized retinal dysfunction predominately central (age related maculopathy) or peripheral (retinitis pigmentosa). Previously we have shown simple eccentricity-only remappings which do not maintain conformality. In this report we present our initial attempts on developing images which hold quasi-conformality after remapping. Although the quasi-conformal images may have less local distortion, there are discontinuities in the image which may counterindicate this type of transformation for the low vision application.
Review of NASA's Evidence Reports on Human Health Risks. 2015 Letter Report
NASA Technical Reports Server (NTRS)
Scott-Conner, Carol E. H.; Masys, Daniel R.; Liverman, Catharyn T.
2016-01-01
NASA has requested a study from the Institute of Medicine (IOM) to provide an independent review of more than 30 evidence reports on human health risks for long duration and exploration spaceflight. The evidence reports, which are publicly available, are categorized into five broad categories: (1) behavioral health and performance; (2) human health countermeasures (with a focus on bone metabolism and orthopedics, nutrition, immunology, and cardiac and pulmonary physiology); (3) radiation; (4) human factors issues; and (5) exploration medical capabilities. The reports are revised on an ongoing basis to incorporate new scientific information. In conducting this study, an IOM ad hoc committee will build on the 2008 IOM report Review of NASA's Human Research Program Evidence Books. That report provided an assessment of the process used for developing the evidence reports and provided an initial review of the evidence reports that had been completed at that time. Each year, NASA staff will identify a set of evidence reports for committee review. Over the course of the study all evidence reports will be reviewed. The committee will hold an annual scientific workshop to receive input on the evidence reports it is reviewing that year and an update on the recent literature. The committee will issue an annual letter report that addresses the following questions relevant to each evidence report: 1. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 2. Does the evidence report make the case for the research gaps presented? 3. Are there any additional gaps in knowledge or areas of fundamental research that should be considered to enhance the basic understanding of this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is input from additional disciplines needed? 6. Is the breadth of the cited literature sufficient? 7. What is the overall readability and quality? 8. Is the expertise of the authors sufficient to fully cover the scope of the given risk? 9. Has the evidence report addressed previous recommendations made by the IOM in the 2008 letter report?
Yoshikawa, Munemitsu; Yamashiro, Kenji; Miyake, Masahiro; Oishi, Maho; Akagi-Kurashige, Yumiko; Kumagai, Kyoko; Nakata, Isao; Nakanishi, Hideo; Oishi, Akio; Gotoh, Norimoto; Yamada, Ryo; Matsuda, Fumihiko; Yoshimura, Nagahisa
2014-10-21
We investigated the association between refractive error in a Japanese population and myopia-related genes identified in two recent large-scale genome-wide association studies. Single-nucleotide polymorphisms (SNPs) in 51 genes that were reported by the Consortium for Refractive Error and Myopia and/or the 23andMe database were genotyped in 3712 healthy Japanese volunteers from the Nagahama Study using HumanHap610K Quad, HumanOmni2.5M, and/or HumanExome Arrays. To evaluate the association between refractive error and recently identified myopia-related genes, we used three approaches to perform quantitative trait locus analyses of mean refractive error in both eyes of the participants: per-SNP, gene-based top-SNP, and gene-based all-SNP analyses. Association plots of successfully replicated genes also were investigated. In our per-SNP analysis, eight myopia gene associations were replicated successfully: GJD2, RASGRF1, BICC1, KCNQ5, CD55, CYP26A1, LRRC4C, and B4GALNT2.Seven additional gene associations were replicated in our gene-based analyses: GRIA4, BMP2, QKI, BMP4, SFRP1, SH3GL2, and EHBP1L1. The signal strength of the reported SNPs and their tagging SNPs increased after considering different linkage disequilibrium patterns across ethnicities. Although two previous studies suggested strong associations between PRSS56, LAMA2, TOX, and RDH5 and myopia, we could not replicate these results. Our results confirmed the significance of the myopia-related genes reported previously and suggested that gene-based replication analyses are more effective than per-SNP analyses. Our comparison with two previous studies suggested that BMP3 SNPs cause myopia primarily in Caucasian populations, while they may exhibit protective effects in Asian populations. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Wanke, Riccardo; Harjivan, Shrika G; Pereira, Sofia A; Marques, M Matilde; Antunes, Alexandra M M
2013-11-01
The potential for co-prescription of the anti-human immunodeficiency virus (anti-HIV) drug efavirenz (EFV) and the oral anticoagulant warfarin (WAR) is currently high as EFV is a drug of choice for HIV type 1 infection and because cardiovascular disease is increasing among HIV-infected individuals. However, clinical reports of EFV-WAR interaction, leading to WAR overdosing, call for elucidation of the mechanisms involved in this drug-drug interaction. Here we present the first report demonstrating competition of the two drugs for the same binding site of human serum albumin. Using ligand-based nuclear magnetic resonance experiments, this study proves that EFV has an effect on the concentration of free WAR. This previously unidentified EFV-WAR interaction represents a potential risk factor that should be taken into account when considering treatment options. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Meteorite falls in China and some related human casualty events
NASA Technical Reports Server (NTRS)
Yau, Kevin; Weissman, Paul; Yeomans, Donald
1994-01-01
Statistics of witnessed and recovered meteorite falls found in Chinese historical texts for the period from 700 B.C. to A.D. 1920 are presented. Several notable features can be seen in the binned distribution as a function of time. An apparent decrease in the number of meteorite reports in the 18th century is observed. An excess of observed meteorite falls in the period from 1840 to 1880 seems to correspond to a similar excess in European data. A chi sq probability test suggest that the association between the two data sets are real. Records of human casualities and structural damage resulting from meteorite falls are also given. A calculation based on the number of casualty events in the Chinese meteorite records suggests that the probability of a meteroite striking a human is far greater than previous estimates. However, it is difficult to verify the accuracy of the reported casualty events.
The hydrogen sulfide metabolite trimethylsulfonium is found in human urine
NASA Astrophysics Data System (ADS)
Lajin, Bassam; Francesconi, Kevin A.
2016-06-01
Hydrogen sulfide is the third and most recently discovered gaseous signaling molecule following nitric oxide and carbon monoxide, playing important roles both in normal physiological conditions and disease progression. The trimethylsulfonium ion (TMS) can result from successive methylation reactions of hydrogen sulfide. No report exists so far about the presence or quantities of TMS in human urine. We developed a method for determining TMS in urine using liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (LC-ESI-QQQ), and applied the method to establish the urinary levels of TMS in a group of human volunteers. The measured urinary levels of TMS were in the nanomolar range, which is commensurate with the steady-state tissue concentrations of hydrogen sulfide previously reported in the literature. The developed method can be used in future studies for the quantification of urinary TMS as a potential biomarker for hydrogen sulfide body pools.
The ammonium sulfate inhibition of human angiogenin.
Chatzileontiadou, Demetra S M; Tsirkone, Vicky G; Dossi, Kyriaki; Kassouni, Aikaterini G; Liggri, Panagiota G V; Kantsadi, Anastassia L; Stravodimos, George A; Balatsos, Nikolaos A A; Skamnaki, Vassiliki T; Leonidas, Demetres D
2016-09-01
In this study, we investigate the inhibition of human angiogenin by ammonium sulfate. The inhibitory potency of ammonium sulfate for human angiogenin (IC50 = 123.5 ± 14.9 mm) is comparable to that previously reported for RNase A (119.0 ± 6.5 mm) and RNase 2 (95.7 ± 9.3 mm). However, analysis of two X-ray crystal structures of human angiogenin in complex with sulfate anions (in acidic and basic pH environments, respectively) indicates an entirely distinct mechanism of inhibition. While ammonium sulfate inhibits the ribonucleolytic activity of RNase A and RNase 2 by binding to the active site of these enzymes, sulfate anions bind only to peripheral substrate anion-binding subsites of human angiogenin, and not to the active site. © 2016 Federation of European Biochemical Societies.
Gao, Peng; Ji, Min; Fang, Xueyan; Liu, Yingyang; Yu, Zhigang; Cao, Yunfeng; Sun, Aijun; Zhao, Liang; Zhang, Yong
2017-11-15
Glioma is one of the most lethal brain malignancies with unknown etiologies. Many metabolomics analysis aiming at diverse kinds of samples had been performed. Due to the varied adopted analytical platforms, the reported disease-related metabolites were not consistent across different studies. Comparable metabolomics results are more likely to be acquired by analyzing the same sample types with identical analytical platform. For tumor researches, tissue samples metabolomics analysis own the unique advantage that it can gain more direct insight into disease-specific pathological molecules. In this light, a previous reported capillary electrophoresis - mass spectrometry human tissues metabolomics analysis method was employed to profile the metabolome of rat C6 cell implantation gliomas and the corresponding precancerous tissues. It was found that 9 metabolites increased in the glioma tissues. Of them, hypotaurine was the only metabolite that enriched in the malignant tissues as what had been reported in the relevant human tissues metabolomics analysis. Furthermore, hypotaurine was also proved to inhibit α-ketoglutarate-dependent dioxygenases (2-KDDs) through immunocytochemistry staining and in vitro enzymatic activity assays by using C6 cell cultures. This study reinforced the previous conclusion that hypotaurine acted as a competitive inhibitor of 2-KDDs and proved the value of metabolomics in oncology studies. Copyright © 2017. Published by Elsevier Inc.
Protothecosis in hematopoietic stem cell transplantation: case report and review of previous cases.
Macesic, N; Fleming, S; Kidd, S; Madigan, V; Chean, R; Ritchie, D; Slavin, M
2014-06-01
Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent individuals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Clogging Transition of Vibration-Driven Vehicles Passing through Constrictions.
Patterson, G A; Fierens, P I; Sangiuliano Jimka, F; König, P G; Garcimartín, A; Zuriguel, I; Pugnaloni, L A; Parisi, D R
2017-12-15
We report experimental results on the competitive passage of elongated self-propelled vehicles rushing through a constriction. For the chosen experimental conditions, we observe the emergence of intermittencies similar to those reported previously for active matter passing through narrow doors. Noteworthy, we find that, when the number of individuals crowding in front of the bottleneck increases, there is a transition from an unclogged to a clogged state characterized by a lack of convergence of the mean clog duration as the measuring time increases. It is demonstrated that this transition-which was reported previously only for externally vibrated systems such as colloids or granulars-appears also for self-propelled agents. This suggests that the transition should also occur for the flow through constrictions of living agents (e.g., humans and sheep), an issue that has been elusive so far in experiments due to safety risks.
Clogging Transition of Vibration-Driven Vehicles Passing through Constrictions
NASA Astrophysics Data System (ADS)
Patterson, G. A.; Fierens, P. I.; Sangiuliano Jimka, F.; König, P. G.; Garcimartín, A.; Zuriguel, I.; Pugnaloni, L. A.; Parisi, D. R.
2017-12-01
We report experimental results on the competitive passage of elongated self-propelled vehicles rushing through a constriction. For the chosen experimental conditions, we observe the emergence of intermittencies similar to those reported previously for active matter passing through narrow doors. Noteworthy, we find that, when the number of individuals crowding in front of the bottleneck increases, there is a transition from an unclogged to a clogged state characterized by a lack of convergence of the mean clog duration as the measuring time increases. It is demonstrated that this transition—which was reported previously only for externally vibrated systems such as colloids or granulars—appears also for self-propelled agents. This suggests that the transition should also occur for the flow through constrictions of living agents (e.g., humans and sheep), an issue that has been elusive so far in experiments due to safety risks.
Unger, Mark D; Pleticha, Josef; Heilmann, Lukas F; Newman, Laura K; Maus, Timothy P; Beutler, Andreas S
2018-05-25
Intrathecal interleukin-10 delivered by plasmid or viral gene vectors has been proposed for clinical testing because it is effective for chronic pain in rodents, a potential therapeutic for various human diseases, and was found to be non-toxic in dogs, when the human interleukin-10 ortholog was tested. However, recent studies in swine testing porcine interleukin-10 demonstrated fatal neurotoxicity. To deliver vector-encoded human interleukin-10 in swine, measure expression of the transgene in cerebrospinal fluid, and monitor animals for signs of neurotoxicity. Human interleukin-10 levels peaked 2 weeks after vector administration followed by a rapid decline that occurred concomitant with the emergence of anti-human interleukin-10 antibodies in the cerebrospinal fluid and serum. Animals remained neurologically healthy throughout the study period. This study suggests that swine are not idiosyncratically sensitive to intrathecal interleukin-10 because, recapitulating previous reports in dogs, they suffered no clinical neurotoxicity from the human ortholog. These results strongly infer that toxicity of intrathecal interleukin-10 in large animal models was previously overlooked because of a species mismatch between transgene and host. The present study further suggests that swine were protected from interleukin-10 by a humoral immune response against the xenogeneic cytokine. Future safety studies of interleukin-10 or related therapeutics may require syngeneic large animal models. This article is protected by copyright. All rights reserved.
The Human Microbiome in the Fight Against Tuberculosis
Wood, Madeleine R.; Yu, Elaine A.; Mehta, Saurabh
2017-01-01
The human microbiome is an intriguing potentially modifiable risk factor in our arsenal against Mycobacterium tuberculosis, the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study (N = 1), case report (N = 1), and case–control studies (N = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case–control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance. PMID:28719264
Lindner, Mark D; Hodges, Donald B; Hogan, John B; Orie, Anitra F; Corsa, Jason A; Barten, Donna M; Polson, Craig; Robertson, Barbara J; Guss, Valerie L; Gillman, Kevin W; Starrett, John E; Gribkoff, Valentin K
2003-11-01
Antagonists of serotonin 6 (5-HT6) receptors have been reported to enhance cognition in animal models of learning, although this finding has not been universal. We have assessed the therapeutic potential of the specific 5-HT6 receptor antagonists 4-amino-N-(2,6-bis-methylamino-pyrimidin-4-yl)-benzenesulfonamide (Ro 04-6790) and 5-chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046) in rodent models of cognitive function. Although mice express the 5-HT6 receptor and the function of this receptor has been investigated in mice, all reports of activity with 5-HT6 receptor antagonists have used rat models. In the present study, receptor binding revealed that the pharmacological properties of the mouse receptor are different from the rat and human receptor: Ro 04-6790 does not bind to the mouse 5-HT6 receptor, so all in vivo testing included in the present report was conducted in rats. We replicated previous reports that 5-HT6 receptor antagonists produce a stretching syndrome previously shown to be mediated through cholinergic mechanisms, but Ro 04-6790 and SB-271046 failed to attenuate scopolamine-induced deficits in a test of contextual fear conditioning. We also failed to replicate the significant effects reported previously in both an autoshaping task and in a version of the Morris water maze. The results of our experiments are not consistent with previous reports that suggested that 5-HT6 antagonists might have therapeutic potential for cognitive disorders.
Cytotoxic components of Pereskia bleo (Kunth) DC. (Cactaceae) leaves.
Malek, Sri Nurestri Abdul; Shin, Sim Kae; Wahab, Norhanom Abdul; Yaacob, Hashim
2009-05-06
Dihydroactinidiolide (1) and a mixture of sterols [campesterol (2), stigmasterol (3) and beta-sitosterol (4)], together with the previously isolated individual compounds beta-sitosterol (4), 2,4-di-tert-butylphenol (5), alpha-tocopherol (6), phytol (7) were isolated from the active ethyl acetate fraction of Pereskia bleo (Kunth) DC. (Cactaceae) leaves. Cytotoxic activities of the above mentioned compounds against five human carcinoma cell lines, namely the human nasopharyngeal epidermoid carcinoma cell line (KB), human cervical carcinoma cell line (CasKi), human colon carcinoma cell line (HCT 116), human hormone-dependent breast carcinoma cell line (MCF7) and human lung carcinoma cell line (A549); and non-cancer human fibroblast cell line (MRC-5) were investigated. Compound 5 possessed very remarkable cytotoxic activity against KB cells, with an IC(50 )value of 0.81microg/mL. This is the first report on the cytotoxic activities of the compounds isolated from Pereskia bleo.
Prosocial behavior leads to happiness in a small-scale rural society.
Aknin, Lara B; Broesch, Tanya; Hamlin, J Kiley; Van de Vondervoort, Julia W
2015-08-01
Humans are extraordinarily prosocial, and research conducted primarily in North America indicates that giving to others is emotionally rewarding. To examine whether the hedonic benefits of giving represent a universal feature of human behavior, we extended upon previous cross-cultural examinations by investigating whether inhabitants of a small-scale, rural, and isolated village in Vanuatu, where villagers have little influence from urban, Western culture, survive on subsistence farming without electricity, and have minimal formal education, report or display emotional rewards from engaging in prosocial (vs. personally beneficial) behavior. In Study 1, adults were randomly assigned to purchase candy for either themselves or others and then reported their positive affect. Consistent with previous research, adults purchasing goods for others reported greater positive emotion than adults receiving resources for themselves. In Study 2, 2- to 5-year-old children received candy and were subsequently asked to engage in costly giving (sharing their own candy with a puppet) and non-costly giving (sharing the experimenter's candy with a puppet). Emotional expressions were video-recorded during the experiment and later coded for happiness. Consistent with previous research conducted in Canada, children displayed more happiness when giving treats away than when receiving treats themselves. Moreover, the emotional rewards of giving were largest when children engaged in costly (vs. non-costly) giving. Taken together, these findings indicate that the emotional rewards of giving are detectable in people living in diverse societies and support the possibility that the hedonic benefits of generosity are universal. (c) 2015 APA, all rights reserved).
Comments on human eurytremiasis in Brazil.
Pinto, Hudson Alves; de Melo, Alan Lane
2016-05-20
Eurytremiasis is an important parasitic disease of cattle that was recently suggested to be a neglected and emerging human disease in Brazil. Based on a misinterpretation of the life cycle of the parasite, it was suggested that a great number of people could be infected with this fluke in the country. In the present letter, aspects of the life cycle of Eurytrema spp. are revisited and clarified. The mechanism of transmission previously reported for the few accidental human cases involved the ingestion of raw or undercooked insects (grasshoppers and crickets) harboring the infective metacercariae. In reality, the zoonotic potential of Eurytrema species is extremely low, and human eurytremiasis is not, and probably never will be, a zoonotic disease in countries where entomophagy is not a common food habit.
Mallick, Tarun K; Mosquera, Alexis; Zinderman, Craig E; St Martin, Laura; Wise, Robert P
2012-06-01
Processors distributed about 1.5 million human tissue allografts in the U.S. in 2007. The potential for transmitting infections through allografts concerns clinicians and patients. In 2005, FDA implemented Current Good Tissue Practice (CGTP) rules requiring tissue establishments to report to FDA certain serious infections after allograft transplantations. We describe infection reports following tissue transplants received by FDA from 2005 through June, 2010, and compare reporting before and after implementation of CGTP rules. We identified reports received by FDA from January 2001 through June, 2010, for infections in human tissue recipients, examining the reports by tissue type, organism, time to onset, severity, and reporter characteristics. Among 562 reports, 83 (20.8/year) were received from 2001-2004, before the CGTP rules, 43 in the 2005 transition year, and 436 (96.9/year) from 2006 through June, 2010, after the rules. Tissue processors accounted for 84.2% of reports submitted after the rules, compared to 26.5% previously. Bacterial infections were the most commonly reported organisms before (64.6%) and after (62.2%) the new rules. Afterward, 2.5% (11) of reports described deaths, and 33.7% (147) involved hospitalizations. Before the rules, 13% (11) described deaths, and another 72% involved hospitalizations. Reports received by the FDA quadrupled since 2005, suggesting that CGTP regulations have contributed to increased reporting and improved tissue safety surveillance. However, these data do not confirm that the reported infections were caused by suspect tissues; most reports may represent routine post-surgical infections not actually due to allografts.
Chang, Hing-Chiu; Sundman, Mark; Petit, Laurent; Guhaniyogi, Shayan; Chu, Mei-Lan; Petty, Christopher; Song, Allen W.; Chen, Nan-kuei
2015-01-01
The advantages of high-resolution diffusion tensor imaging (DTI) have been demonstrated in a recent post-mortem human brain study (Miller et al., NeuroImage 2011;57(1):167–181), showing that white matter fiber tracts can be much more accurately detected in data at submillimeter isotropic resolution. To our knowledge, in vivo human brain DTI at submillimeter isotropic resolution has not been routinely achieved yet because of the difficulty in simultaneously achieving high resolution and high signal-to-noise ratio (SNR) in DTI scans. Here we report a 3D multi-slab interleaved EPI acquisition integrated with multiplexed sensitivity encoded (MUSE) reconstruction, to achieve high-quality, high-SNR and submillimeter isotropic resolution (0.85 × 0.85 × 0.85 mm3) in vivo human brain DTI on a 3 Tesla clinical MRI scanner. In agreement with the previously reported post-mortem human brain DTI study, our in vivo data show that the structural connectivity networks of human brains can be mapped more accurately and completely with high-resolution DTI as compared with conventional DTI (e.g., 2 × 2 × 2 mm3). PMID:26072250
Escaffre, Olivier; Borisevich, Viktoriya; Vergara, Leoncio A; Wen, Julie W; Long, Dan; Rockx, Barry
2016-05-01
Nipah virus (NiV) is an emerging paramyxovirus that can cause lethal respiratory illness in humans. No vaccine/therapeutic is currently licensed for humans. Human-to-human transmission was previously reported during outbreaks and NiV could be isolated from respiratory secretions, but the proportion of cases in Malaysia exhibiting respiratory symptoms was significantly lower than that in Bangladesh. Previously, we showed that primary human basal respiratory epithelial cells are susceptible to both NiV-Malaysia (M) and -Bangladesh (B) strains causing robust pro-inflammatory responses. However, the cells of the human respiratory epithelium that NiV targets are unknown and their role in NiV transmission and NiV-related lung pathogenesis is still poorly understood. Here, we characterized NiV infection of the human respiratory epithelium using a model of the human tracheal/bronchial (B-ALI) and small airway (S-ALI) epithelium cultured at an air-liquid interface. We show that NiV-M and NiV-B infect ciliated and secretory cells in B/S-ALI, and that infection of S-ALI, but not B-ALI, results in disruption of the epithelium integrity and host responses recruiting human immune cells. Interestingly, NiV-B replicated more efficiently in B-ALI than did NiV-M. These results suggest that the human tracheal/bronchial epithelium is favourable to NiV replication and shedding, while inducing a limited host response. Our data suggest that the small airways epithelium is prone to inflammation and lesions as well as constituting a point of virus entry into the pulmonary vasculature. The use of relevant models of the human respiratory tract, such as B/S-ALI, is critical for understanding NiV-related lung pathogenesis and identifying the underlying mechanisms allowing human-to-human transmission.
Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples are expressed at the protein level. The integration of proteomic and genomic data, or proteogenomics, provides a more comprehensive view of the biological features that drive cancer than genomic analysis alone and may help identify the most important targets for cancer detection and intervention.
Ford, Dayton J; Ropka, Stacie L; Collins, George H; Jubelt, Burk
2002-09-01
Human paralytic poliomyelitis results from the destruction of spinal cord anterior horn motor neurons by human poliovirus (PV). CNS disease pathology similar to human poliomyelitis has been observed in experimentally infected chimpanzees, monkeys and wild-type mice. In this study we present a detailed examination of the clinical and histopathological features in the wild-type mouse after intracranial (i.c.) and novel intramuscular (i.m.) injection of poliovirus. Either route of poliovirus administration results in a clinical disease characterized predominately by flaccid paralysis. The observed histopathological features are compared with the histopathology reported for human paralytic poliomyelitis, experimentally infected chimpanzees, monkeys and transgenic mice expressing the human poliovirus receptor (hPVR). The observation of flaccid paralysis and anterior horn motor neuron destruction mirrors what is observed in human paralytic poliomyelitis. Our results suggest that the neuropathology observed in the wild-type mouse model is similar to what has been observed in both the human disease and in other experimental animal models, with the possible exception of the transgenic mouse model. The observed neuropathology of the wild-type mouse model more closely reflects what has been observed in human poliomyelitis, as well as in experimentally infected chimpanzees and monkeys, than does the hPVR transgenic mouse model. The previously reported poliovirus-induced white matter demyelinating disease was not observed.
This study was motivated by a previous report of associations between episodes of high air pollution and alterations in semen quality in young men living in an industrial district of the Czech Republic. Using a repeated measures study design, a cohort of men from this district we...
USDA-ARS?s Scientific Manuscript database
Escherichia coli O157 (O157) persist at the recto-anal junction (RAJ) of gastrointestinal tracts (GIT) of cattle, the primary reservoirs of this human pathogen. We recently reported (Kudva et al., BMC Microbiol. 2012, 12: 103) that the previously identified and extensively documented principal O157...
Klitgaard, Kirstine; Chriél, Mariann; Isbrand, Anastasia; Jensen, Tim K.
2017-01-01
From a migrating golden jackal (Canis aureus), we retrieved 21 live male Dermacentor reticulatus ticks, a species not previously reported from wildlife in Denmark. We identified Rickettsia raoultii from 18 (86%) of the ticks. This bacterium is associated with scalp eschar and neck lymphadenopathy after tick bite syndrome among humans. PMID:29148376
ERIC Educational Resources Information Center
Sessions, Joan T.; Yanos, Janet Hagan
This study sought to identify characteristics of counselors and counseling services that are important in the selection of a counseling service. Subjects (N=28) were recruited through a newspaper advertisement and through mall intercepts. The screening criteria were designed to locate potential or previous counseling service consumers whose…
Torres-Pérez, Fernando; Palma, R. Eduardo; Hjelle, Brian; Ferres, Marcela; Cook, Joseph A.
2009-01-01
Hantavirus cardiopulmonary syndrome (HCPS) is an emerging infectious disease first reported in Chile in 1995. Andes hantavirus (ANDV) is responsible for the more than 500 cases of HCPS reported in Chile. Previous work showed that ANDV is genetically differentiated in Chile across contrasting landscapes. To determine whether the reservoir rodent (Oligoryzomys longicaudatus) populations are also geographically segregated, we conducted range-wide spatial genetic analyses of O. longicaudatus in Chile using the mitochondrial DNA cytochrome b gene. Given that landscape structure influences the incidence of hantavirus infections, we also tested 772 O. longicaudatus specimens for antibodies to ANDV captured during the period 2000 − 2006. Population genetic analyses of O. longicaudatus are largely congruent with those reported for ANDV, with the host primarily differentiated according to three defined ecoregions, Mediterranean, Valdivian rain forest and North Patagonian rain forest. Significant differences in the relative prevalence of anti-ANDV antibodies in rodent samples also were found across the three ecoregions. We relate these results to the number of reported human HCPS cases in Chile, and discuss the importance of landscape differences in light of ANDV transmission to humans and among rodent populations. PMID:19632357
A historical reflection on the discovery of human retroviruses.
Vahlne, Anders
2009-05-01
The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I) was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1) was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984.
Johnson, Darryl; Carter, Melissa D.; Crow, Brian S.; Isenberg, Samantha L.; Graham, Leigh Ann; Erol, H. Akin; Watson, Caroline M.; Pantazides, Brooke G.; van der Schans, Marcel J.; Langenberg, Jan P.; Noort, Daan; Blake, Thomas A.; Thomas, Jerry D.; Johnson, Rudolph C.
2017-01-01
Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids, and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to form the aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic-UHPLC-MS/MS method for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. The method has a reportable range from 2.0 ng/mL to 150 ng/mL, which is consistent with the sensitivity of methods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥ 85%) and precision (RSD ≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72 hours at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20, and demonstrates a 3-fold improvement in sensitivity. PMID:26149113
Shiraishi, H; Ishikura, S; Matsuura, K; Deyashiki, Y; Ninomiya, M; Sakai, S; Hara, A
1998-01-01
Human liver contains three isoforms (DD1, DD2 and DD4) of dihydrodiol dehydrogenase with 20alpha- or 3alpha-hydroxysteroid dehydrogenase activity; the dehydrogenases belong to the aldo-oxo reductase (AKR) superfamily. cDNA species encoding DD1 and DD4 have been identified. However, four cDNA species with more than 99% sequence identity have been cloned and are compatible with a partial amino acid sequence of DD2. In this study we have isolated a cDNA clone encoding DD2, which was confirmed by comparison of the properties of the recombinant and hepatic enzymes. This cDNA showed differences of one, two, four and five nucleotides from the previously reported four cDNA species for a dehydrogenase of human colon carcinoma HT29 cells, human prostatic 3alpha-hydroxysteroid dehydrogenase, a human liver 3alpha-hydroxysteroid dehydrogenase-like protein and chlordecone reductase-like protein respectively. Expression of mRNA species for the five similar cDNA species in 20 liver samples and 10 other different tissue samples was examined by reverse transcriptase-mediated PCR with specific primers followed by diagnostic restriction with endonucleases. All the tissues expressed only one mRNA species corresponding to the newly identified cDNA for DD2: mRNA transcripts corresponding to the other cDNA species were not detected. We suggest that the new cDNA is derived from the principal gene for DD2, which has been named AKR1C2 by a new nomenclature for the AKR superfamily. It is possible that some of the other cDNA species previously reported are rare allelic variants of this gene. PMID:9716498
Korn, Christoph W; Vunder, Johanna; Miró, Júlia; Fuentemilla, Lluís; Hurlemann, Rene; Bach, Dominik R
2017-10-01
Rodent approach-avoidance conflict tests are common preclinical models of human anxiety disorder. Their translational validity mainly rests on the observation that anxiolytic drugs reduce rodent anxiety-like behavior. Here, we capitalized on a recently developed approach-avoidance conflict computer game to investigate the impact of benzodiazepines and of amygdala lesions on putative human anxiety-like behavior. In successive epochs of this game, participants collect monetary tokens on a spatial grid while under threat of virtual predation. In a preregistered, randomized, double-blind, placebo-controlled trial, we tested the effect of a single dose (1 mg) of lorazepam (n = 59). We then compared 2 patients with bilateral amygdala lesions due to Urbach-Wiethe syndrome with age- and gender-matched control participants (n = 17). Based on a previous report, the primary outcome measure was the effect of intra-epoch time (i.e., an adaptation to increasing potential loss) on presence in the safe quadrant of the spatial grid. We hypothesized reduced loss adaptation in this measure under lorazepam and in patients with amygdala lesions. Lorazepam and amygdala lesions reduced loss adaptation in the primary outcome measure. We found similar results in several secondary outcome measures. The relative reduction of anxiety-like behavior in patients with amygdala lesions was qualitatively and quantitatively indistinguishable from an impact of anterior hippocampus lesions found in a previous report. Our results establish the translational validity of human approach-avoidance conflict tests in terms of anxiolytic drug action. We identified the amygdala, in addition to the hippocampus, as a critical structure in human anxiety-like behavior. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Molecular characteristics of "Mycobacterium canettii" the smooth Mycobacterium tuberculosis bacilli.
Fabre, Michel; Hauck, Yolande; Soler, Charles; Koeck, Jean-Louis; van Ingen, Jakko; van Soolingen, Dick; Vergnaud, Gilles; Pourcel, Christine
2010-12-01
Since the first discovery of the smooth tubercle (SmTB) bacilli "Mycobacterium canettii" less than 60 isolates have been reported, all but one originating from a limited geographical location, the Horn of Africa. In spite of its rarity, the SmTB lineage deserves special attention. Previous investigations suggested that SmTB isolates represent an ancestral lineage of the Mycobacterium tuberculosis complex (MTBC) and that consequently they might provide essential clues on the origin and evolution of the MTBC. There is evidence that unlike the rest of the MTBC, SmTB strains recombine chromosomal sequences with a yet unknown Mycobacterium species. This behavior contributes to the much larger genetic heterogeneity observed in the SmTB isolates compared to the other members of the MTBC. We have collected 59 SmTB isolates of which 14 were newly recovered since previous reports, and performed extensive phenotypical and genotypical characterization. We take advantage of these investigations to review the current knowledge of "M. canettii". Their characteristics and the apparent lack of human to human transmission are consistent with the previously proposed existence of non-human sources of infection. SmTB strains show remarkably common features together with secondary and taxonomically minor genetic differences such as the presence or absence of the CRISPR (Clustered Regularly Interspersed Palindromic Repeat) locus (usually called Direct Repeat or DR region) or number of IS sequences. Multiple Locus Variable number of tandem repeat Analysis (MLVA) and DR region analyses reveal one predominant clone, one minor clone and a number of more distantly related strains. This suggests that the two most frequent clones may represent successfully emerging lineages. Copyright © 2010 Elsevier B.V. All rights reserved.
Qi, Li; Su, Kun; Shen, Tao; Tang, Wenge; Xiao, Bangzhong; Long, Jiang; Zhao, Han; Chen, Xi; Xia, Yu; Xiong, Yu; Xiao, Dayong; Feng, Liangui; Li, Qin
2018-01-03
According to the global framework of eliminating human rabies, China is responding to achieve the target of zero human death from dog-mediated rabies by 2030. Chongqing is the largest municipality directly under central government in China. We described the epidemiological characteristics and post-exposure prophylaxis (PEP) of human rabies in this area, in order to provide a reliable epidemiology basis for further control and prevention of human rabies. The most updated epidemiological data for human rabies cases from 2007 to 2016 in Chongqing were collected from the National Disease Reporting Information System. A standardized questionnaire was applied to the human rabies cases or family members of cases as proxy to investigate the PEP situation. A total of 809 fatal human rabies cases were reported in Chongqing from 2007 to 2016. There was a trend of gradual annual decline about number of cases from 2007 to 2013, followed by stable levels until 2016. Rabies was mostly reported in summer and autumn; a majority of cases were noted in farmers (71.8%), especially in males (65.3%). The cases aged 35-74 and 5-14 years old accounted for 83.8% of all the cases. We collected information of 548 human rabies cases' rabies exposure and PEP situation. Of those, 95.8% of human rabies cases were victims of dog bites or scratch, and 53.3% of these dogs were identified as stray dogs. Only 4.0% of the domestic dogs were reported to have been vaccinated previously. After exposure, 87.8% of the 548 human rabies cases did not seek any medical services. Further investigation showed that none of the 548 cases received timely and properly standardized PEP. Human rabies remains a major public health problem in Chongqing, China. Dogs are the main reservoir and source of human rabies infection. Unsuccessful control of canine rabies and inadequate PEP of cases might be the main factors leading to the serious human rabies epidemic in this area. An integrated "One Health" approach should be encouraged and strengthened in this area; with combined effort it would be possible to achieve the elimination of human rabies in the expected date.
Tong, L J; Flach, E J; Sheppard, M N; Pocknell, A; Banerjee, A A; Boswood, A; Bouts, T; Routh, A; Feltrer, Y
2014-07-01
Cardiovascular disease is increasingly recognized as an important cause of morbidity and mortality in captive chimpanzees (Pan troglodytes). This report records 2 cases of sudden cardiac death in closely related subadult captive chimpanzees with marked replacement fibrosis and adipocyte infiltration of the myocardium, which resemble specific atypical forms of the familial human disease arrhythmogenic right ventricular cardiomyopathy. Changes were consistent with left-dominant and biventricular subtypes, which are both phenotypic variants found within human families with familial arrhythmogenic right ventricular cardiomyopathy. Previously reported fibrosing cardiomyopathies in chimpanzees were characterized by nonspecific interstitial fibrosis, in contrast to the replacement fibrofatty infiltration with predilection for the outer myocardium seen in these 2 cases. To the authors' knowledge, this case report is the first to describe cardiomyopathy resembling arrhythmogenic right ventricular cardiomyopathy in nonhuman primates and the first to describe left-dominant arrhythmogenic cardiomyopathy-type lesions in an animal. © The Author(s) 2013.
An Evaluation of Evidence for the Carcinogenic Activity of Bisphenol A
Keri, Ruth A.; Ho, Shuk-Mei; Hunt, Patricia A.; Knudsen, Karen E.; Soto, Ana M.; Prins, Gail S.
2008-01-01
The National Institutes of Health (NIEHS, NIDCR) and the United States Environmental Protection Agency convened an expert panel of scientists with experience in the field of environmental endocrine disruptors, particularly with knowledge and research on Bisphenol A (BPA). Five subpanels were charged to review the published literature and previous reports in five specific areas and to compile a consensus report with recommendations. These were presented and discussed at an open forum entitled “Bisphenol A: An Expert Panel Examination of the Relevance of Ecological, In Vitro and Laboratory Animal Studies for Assessing Risks to Human Health” in Chapel Hill, NC on November 28-30, 2006. The present review consists of the consensus report on the evidence for a role of BPA in carcinogenesis, examining the available evidence in humans and animal models with recommendations for future areas of research. PMID:17706921
Formant characteristics of human laughter.
Szameitat, Diana P; Darwin, Chris J; Szameitat, André J; Wildgruber, Dirk; Alter, Kai
2011-01-01
Although laughter is an important aspect of nonverbal vocalization, its acoustic properties are still not fully understood. Extreme articulation during laughter production, such as wide jaw opening, suggests that laughter can have very high first formant (F(1)) frequencies. We measured fundamental frequency and formant frequencies of the vowels produced in the vocalic segments of laughter. Vocalic segments showed higher average F(1) frequencies than those previously reported and individual values could be as high as 1100 Hz for male speakers and 1500 Hz for female speakers. To our knowledge, these are the highest F(1) frequencies reported to date for human vocalizations, exceeding even the F(1) frequencies reported for trained soprano singers. These exceptionally high F(1) values are likely to be based on the extreme positions adopted by the vocal tract during laughter in combination with physiological constraints accompanying the production of a "pressed" voice. Copyright © 2011 The Voice Foundation. All rights reserved.
Mahmoudi, S; Zaini, F
2015-01-01
Sporotrichosis is a chronic subcutaneous fungal infection with global distribution. It is a rare fungal infection with nine reported cases in Iran, including eight humans and one animal, within the past 30 years. Among the human cases, seven were of the fixed cutaneous type of sporotrichosis and one had sporotrichoid lymphocutaneous. The reported patients were within the age range of 23-60 years, and six of them were female. The most frequent sites of infection were forearms and hands, as well as the face and legs. In addition, the majority of the cases had previously been suspected of leishmaniasis and received treatment. Sporotrichosis is not a well-known condition in Iran and is often misdiagnosed and erroneously treated for other cutaneous parasitic or bacterial infections with similar clinical manifestations. Therefore, sporotrichosis should be taken into account in the differential diagnosis of nodular-ulcerative skin lesions. PMID:28680987
Cammarata-Scalisi, Francisco; Cozar, Mónica; Grinberg, Daniel; Balcells, Susana; Asteggiano, Carla G; Martínez-Domenech, Gustavo; Bracho, Ana; Sánchez, Yanira; Stock, Frances; Delgado-Luengo, Wilmer; Zara-Chirinos, Carmen; Chacín, José Antonio
2015-04-01
Hereditary forms of multiple exostoses, now called EXT1/EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilage-capped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the disease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18,000 to 1/50,000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses.
Hsu, Emory; Phadke, Varun K; Nguyen, Minh Ly T
2016-06-01
We describe an HIV-infected patient initiated on combined antiretroviral therapy (cART) who subsequently developed immune restoration disease (IRD) hyperthyroidism-this case represents one of five such patients seen at our center within the past year. Similar to previous reports of hyperthyroidism due to IRD, all of our patients experienced a rapid early recovery in total CD4 count, but developed symptoms of hyperthyroidism on average 3 years (38 months) after beginning cART, which represents a longer time frame than previously reported. Awareness and recognition of this potential complication of cART, which may occur years after treatment initiation, will allow patients with immune restorative hyperthyroidism to receive timely therapy and avoid the long-term complications associated with undiagnosed thyroid disease.
Migou, S; Hashizume, M; Tsugawa, K; Kishihara, F; Kawanaka, H; Ohta, M; Tanoue, K; Kuroiwa, T; Kawamoto, K; Sugimachi, K
1998-01-01
This report describes a 38-year-old man with massive gastrointestinal bleeding from jejunal varices. He had been previously diagnosed to have idiopathic portal hypertension and esophageal varices, and had undergone an esophageal transection 8 years earlier. The pre-operative diagnosis was a suspected hemorrhage from the small intestine as visualized by 99mTc-HSAD scintigraphy (technetium 99m-labeled human serum albumin D-type) and was not considered to be repeated massive lower GI tract bleeding. An exploratory laparotomy was performed, and intra-operative endoscopy revealed active bleeding from the jejunal varices. A partial resection of the small intestine resulted in a complete resolution of the bleeding. A review of the literature thereafter disclosed twelve previously reported cases of jejunal variceal bleeding.
Cerebral Candidal Abscess and Bovine Viral Diarrhoea Virus Infection in an Aborted Bovine Fetus.
Vilander, A C; Niles, G A; Frank, C B
2016-01-01
Candida species are opportunistic fungi associated with immunosuppression and are the most commonly isolated fungal pathogens from the human central nervous system. Invasive candidiasis is reported uncommonly in animals and there have only been two reports of candidal infection of the brain. This report presents a case of a cerebral candidal abscess in an aborted late-term calf co-infected with bovine viral diarrhoea virus. Candida etchellsii, a species not previously identified as pathogenic, was identified as the causative agent by polymerase chain reaction. Copyright © 2016 Elsevier Ltd. All rights reserved.
Envenomation by the Northern Blacktail Rattlesnake (Crotalus molossus molossus): case report.
Yarema, Mark C; Curry, Steven C
2005-01-01
The clinical course after a human envenomation by the Northern Blacktail rattlesnake (Crotalus molossus molossus) is not well described in the literature. The present report discusses a 12-year-old girl who was envenomated by C. molossus molossus and treated with antivenom (Crotalidae polyvalent immune Fab). Her recovery was uncomplicated, and she was discharged after 48 hours of hospitalization. Hematologic and coagulation studies were within normal limits at follow up. The clinical effects of C. molossus molossus envenomation are reviewed, and previous reports of bites by C. molossus molossus are discussed and compared with our patient.
Rabies surveillance in the United States during 2009.
Blanton, Jesse D; Palmer, Dustyn; Rupprecht, Charles E
2010-09-15
During 2009, 49 states and Puerto Rico reported 6,690 rabid animals and 4 human rabies cases to the CDC, representing a 2.2% decrease from the 6,841 rabid animals and 2 human cases reported in 2008. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,327 (34.8%) raccoons, 1,625 (24.3%) bats, 1,603 (24.0%) skunks, 504 (75%) foxes, 300 (4.5%) cats, 81 (1.2%) dogs, and 74 (1.1%) cattle. Compared with 2008, numbers of rabid raccoons and bats that were reported decreased, whereas numbers of rabid skunks, foxes, cats, cattle, dogs, and horses that were reported increased. Fewer rabid raccoons, compared with 2008, were reported by 12 of the 20 eastern states where raccoon rabies is enzootic, and number of rabid raccoons decreased by 2.6% overall nationally. Despite a 10% decrease in the number of rabid bats that were reported and a decrease in the total number of bats submitted for testing, bats were the second most commonly submitted animal, behind cats, during 2009. The number of rabid skunks that were reported increased by 0.9% overall. The proportion of rabid skunks in which infection was attributed to the raccoon rabies virus variant decreased from 473% in 2008 to 40.9% in 2009, resulting in a 12.7% increase in the number of rabid skunks infected with a skunk rabies virus variant. The number of rabid foxes increased 11.0% overall from the previous year. Four cases of rabies involving humans were reported from Texas, Indiana, Virginia, and Michigan. The Texas case represented the first presumptive abortive human rabies case, with the patient recovering after the onset of symptoms without intensive care. The Indiana and Michigan cases were associated with bat rabies virus variants. The human rabies case in Virginia was associated with a canine rabies virus variant acquired during the patient's travel to India.
Common themes and cell type specific variations of higher order chromatin arrangements in the mouse
Mayer, Robert; Brero, Alessandro; von Hase, Johann; Schroeder, Timm; Cremer, Thomas; Dietzel, Steffen
2005-01-01
Background Similarities as well as differences in higher order chromatin arrangements of human cell types were previously reported. For an evolutionary comparison, we now studied the arrangements of chromosome territories and centromere regions in six mouse cell types (lymphocytes, embryonic stem cells, macrophages, fibroblasts, myoblasts and myotubes) with fluorescence in situ hybridization and confocal laser scanning microscopy. Both species evolved pronounced differences in karyotypes after their last common ancestors lived about 87 million years ago and thus seem particularly suited to elucidate common and cell type specific themes of higher order chromatin arrangements in mammals. Results All mouse cell types showed non-random correlations of radial chromosome territory positions with gene density as well as with chromosome size. The distribution of chromosome territories and pericentromeric heterochromatin changed during differentiation, leading to distinct cell type specific distribution patterns. We exclude a strict dependence of these differences on nuclear shape. Positional differences in mouse cell nuclei were less pronounced compared to human cell nuclei in agreement with smaller differences in chromosome size and gene density. Notably, the position of chromosome territories relative to each other was very variable. Conclusion Chromosome territory arrangements according to chromosome size and gene density provide common, evolutionary conserved themes in both, human and mouse cell types. Our findings are incompatible with a previously reported model of parental genome separation. PMID:16336643
Buckmaster, Paul S; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M D; Van Bonn, William
2014-05-01
California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy. Copyright © 2013 Wiley Periodicals, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stroemstedt, P.E.B.; Berkenstam, A.; Joernvall, H.G.
1990-08-05
Partially purified preparations of the human progestin receptor and the human and rat glucocorticoid receptor proteins were covalently charged with the synthetic progestin, ({sup 3}H)promegestone, by photoaffinity labeling. After labeling, the denaturated protein was cleaved and the mixture of peptides subjected to radiosequence analysis as previously described for the rat glucocorticoid receptor protein. The radioactivity labels identified, corresponded to Met-759 and Met-909 after photoaffinity labeling of the human progestin receptor, and Met-622 and Cys-754 after labeling of the rat glucocorticoid receptor. The residues labeled in the glucocorticoid receptor are the same as those previously reported to bind triamcinolone actonide. Themore » corresponding residues were also labeled in the human glucocorticoid receptor. Met-759 of the progestin receptor and Met-622 of the rat glucocorticoid receptor are positioned within a segment with an overall high degree of sequence similarity and are equivalent. However, Met-909 (progestin receptor) and Cys-754 (glucocorticoid receptor) do not occur within equivalent segments of the two proteins. Thus, although the two classes of steroid hormone share a common structure within the A-ring, there are subtle differences in their interaction with the two separate receptor proteins.« less
Landis, B N; Grouzmann, E; Monod, M; Busso, N; Petak, F; Spiliopoulos, A; Robert, J H; Szalay-Quinodoz, I; Morel, D R; Lacroix, J S
2008-01-01
Decreased dipeptidylpeptidase IV (DPPIV) activity within the human nasal mucosa has previously been shown to contribute to the severity of chronic inflammatory rhinosinusitis. To investigate and correlate the role of DPPIV activity with regard to bronchial inflammation. DPPIV/CD26 activity/concentration was investigated in the bronchial tissue of human subjects suffering from chronic bronchial inflammation. In addition, the effect of a recombinant Aspergillus fumigatus DPPIV (fuDPPIV) was investigated on histamine-induced bronchoconstriction in anesthetized rabbits. DPPIV/CD26 was present in submucosal seromucous glands, in leukocytes and to a very low degree in endothelial cells of human bronchi. DPPIV activity was correlated with tissue CD26 content measured by immunoassay. As previously reported for the nasal mucosa, DPPIV/CD26 activity was inversely correlated with the degree of airway inflammation. Systemic pretreatment with recombinant fuDPPIV markedly reduced the increase in histamine-induced airway resistance in rabbits. In conclusion, DPPIV activity modulates lower airway tone by degrading unknown peptidic substrates released by histamine in response to an allergen. Contrasting with our observations in the nose, this modulation is apparently not mediated via a neurokinin (NK1) receptor. (c) 2007 S. Karger AG, Basel.
Arzouni, Ahmed A; Vargas-Seymour, Andreia; Rackham, Chloe L; Dhadda, Paramjeet; Huang, Guo-Cai; Choudhary, Pratik; Nardi, Nance; King, Aileen J F; Jones, Peter M
2017-12-01
The aims of the present study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pre-treated with its products - extracellular matrix (ECM) and annexin A1 (ANXA1). Mouse islets were pre-treated with mouse MSC-derived ECM. Islet insulin secretory function was assessed in vitro by radioimmunoassay. Quantitative RT-PCR was used to screen human adipMSCs for potential ligands of human islet G-protein-coupled receptors. We show that co-culture with hASCs improves human islet secretory function in vitro , as measured by glucose-stimulated insulin secretion, confirming previous reports using rodent tissues. Furthermore, we demonstrate that these beneficial effects on islet function can be partly attributed to the MSC-derived products ECM and ANXA1. Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Generation of a transplantable erythropoietin-producer derived from human mesenchymal stem cells.
Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Ohashi, Toya; Sado, Yoshikazu; Suzuki, Hideaki; Kawamura, Tetsuya; Okabe, Masataka; Hosoya, Tatsuo; Kobayashi, Eiji
2008-06-15
Differentiation of autologous stem cells into functional transplantable tissue for organ regeneration is a promising regenerative therapeutic approach for cancer, diabetes, and many human diseases. Yet to be established, however, is differentiation into tissue capable of producing erythropoietin (EPO), which has a critical function in anemia. We report a novel EPO-producing organ-like structure (organoid) derived from human mesenchymal stem cells. Using our previously established relay culture system, a human mesenchymal stem cell-derived, human EPO-competent organoid was established in rat omentum. The organoid-derived levels of human EPO increased in response to anemia induced by rapid blood withdrawal. In addition, the presence of an organoid in rats suppressed for native (rat) EPO production enhanced recovery from anemia when compared with control animals lacking the organoid. Together these results confirmed the generation of a stem cell-derived organoid that is capable of producing EPO and sensitive to physiological regulation.
Chin, Alex W H; Mok, Chris K P; Zhu, Huachen; Guan, Yi; Peiris, Joseph S M; Poon, Leo L M
2014-09-01
Avian H7N9 influenza viruses may pose a further threat to humans by reassortment with human viruses, which could lead to generation of novel reassortants with enhanced polymerase activity. We previously established a novel statistical approach to study the polymerase activity of reassorted vRNPs (Influenza Other Respir Viruses. 2013;7:969-78). Here, we report the use of this method to study recombinant vRNPs with subunits derived from human H1N1, H3N2, and H7N9 viruses. Our results demonstrate that some reassortant vRNPs with subunits derived from the H7N9 and other human viruses can have much higher polymerase activities than the wild-type levels. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
Campolmi, Irene; Spinicci, Michele; Mayaregua, David Rojo; Barahona, Herlan Gamboa; Mantella, Antonia; Lara, Yunni; Roselli, Mimmo; Strohmeyer, Marianne; Corti, Giampaolo; Tolari, Francesco; Pinckert, Joaquín Monasterio; Dalton, Harry R; Bartoloni, Alessandro
2018-05-01
In the Bolivian Chaco, south-east of Bolivia, studies conducted over the past three decades reported hepatitis A virus (HAV) and Helicobacter pylori seroprevalences above 90% and 60%, respectively. Hepatitis E virus (HEV) prevalence was previously found to be 6-7% but is probably an underestimate because of the poor sensitivity of the assays used. In November 2013, we conducted a cross-sectional study of 263 healthy volunteers from two rural communities of the Bolivian Chaco, aiming to reassess HAV, HEV, and H. pylori seroprevalence 10-20 years following the previous surveys. Hepatitis A virus seroprevalence was 95%, with universal exposure after the first decade of life; HEV seroprevalence was considerably higher (31-35%) than that previously reported; H. pylori seroprevalence was 59%, with an age-dependent distribution. The high prevalence of these infections suggests that major efforts are still needed to reduce fecal-oral transmission and to improve human health in the Bolivian Chaco.
Russell, Jamie L; Lyn, Heidi; Schaeffer, Jennifer A; Hopkins, William D
2011-11-01
The cultural intelligence hypothesis (CIH) claims that humans' advanced cognition is a direct result of human culture and that children are uniquely specialized to absorb and utilize this cultural experience (Tomasello, 2000). Comparative data demonstrating that 2.5-year-old human children outperform apes on measures of social cognition but not on measures of physical cognition support this claim (Herrmann et al., 2007). However, the previous study failed to control for rearing when comparing these two species. Specifically, the human children were raised in a human culture whereas the apes were raised in standard sanctuary settings. To further explore the CIH, here we compared the performance on multiple measures of social and physical cognition in a group of standard reared apes raised in conditions typical of zoo and biomedical laboratory settings to that of apes reared in an enculturated socio-communicatively rich environment. Overall, the enculturated apes significantly outperformed their standard reared counterparts on the cognitive tasks and this was particularly true for measures of communication. Furthermore, the performance of the enculturated apes was very similar to previously reported data from 2.5-year-old children. We conclude that apes who are reared in a human-like socio-communicatively rich environment develop superior communicative abilities compared to apes reared in standard laboratory settings, which supports some assumptions of the cultural intelligence hypothesis. 2011 Blackwell Publishing Ltd.
Evans, Joyce J; Bohnsack, John F; Klesius, Phillip H; Whiting, April A; Garcia, Julio C; Shoemaker, Craig A; Takahashi, Shinji
2008-11-01
Streptococcus agalactiae, commonly known as group B streptococcus (GBS), is a cause of infectious disease in numerous animal species. This study examined the genetic relatedness of piscine, dolphin and human GBS isolates and bovine GBS reference strains from different geographical regions using serological and molecular serotyping and multilocus sequence typing (MLST) techniques. Piscine isolates originating from Kuwait, Brazil, Israel and the USA were capsular serotype Ia, a serotype previously unreported in GBS isolated from fish. Sequence typing of piscine isolates produced six sequence types (ST-7, ST-257, ST-258, ST-259, ST-260 and ST-261), the latter five representing allelic designations and allelic combinations not previously reported in the S. agalactiae MLST database. Genomic diversity existed between dolphin and piscine GBS isolates from Kuwait and other geographical areas. Piscine GBS isolates from Brazil, Israel, Honduras and the USA appeared to represent a distinct genetic population of strains that were largely unrelated to human and bovine GBS. The Kuwait dolphin and piscine lineage (ST-7, Ia) was also associated with human neonatal infections in Japan. Comparative genomics of piscine, human and bovine GBS could help clarify those genes important for host tropism, the emergence of unique pathogenic clones and whether these hosts act as reservoirs of one another's pathogenic lineages.
The evolution of human phenotypic plasticity: age and nutritional status at maturity.
Gage, Timothy B
2003-08-01
Several evolutionary optimal models of human plasticity in age and nutritional status at reproductive maturation are proposed and their dynamics examined. These models differ from previously published models because fertility is not assumed to be a function of body size or nutritional status. Further, the models are based on explicitly human demographic patterns, that is, model human life-tables, model human fertility tables, and, a nutrient flow-based model of maternal nutritional status. Infant survival (instead of fertility as in previous models) is assumed to be a function of maternal nutritional status. Two basic models are examined. In the first the cost of reproduction is assumed to be a constant proportion of total nutrient flow. In the second the cost of reproduction is constant for each birth. The constant proportion model predicts a negative slope of age and nutritional status at maturation. The constant cost per birth model predicts a positive slope of age and nutritional status at maturation. Either model can account for the secular decline in menarche observed over the last several centuries in Europe. A search of the growth literature failed to find definitive empirical documentation of human phenotypic plasticity in age and nutritional status at maturation. Most research strategies confound genetics with phenotypic plasticity. The one study that reports secular trends suggests a marginally insignificant, but positive slope. This view tends to support the constant cost per birth model.
The impact of globalisation on the distribution of Echinococcus multilocularis.
Davidson, Rebecca K; Romig, Thomas; Jenkins, Emily; Tryland, Morten; Robertson, Lucy J
2012-06-01
In the past three decades, Echinococcus multilocularis, the cause of human alveolar echinococcosis, has been reported in several new countries both in definitive hosts (canids) as well as in people. Unless treated, infection with this cestode in people is fatal. In previously endemic countries throughout the Northern Hemisphere, geographic ranges and human and animal prevalence levels seem to be increasing. Anthropogenic influences, including increased globalisation of animals and animal products, and altered human/animal interfaces are thought to play a vital role in the global emergence of this pathogenic cestode. Molecular epidemiological techniques are a useful tool for detecting and tracing introductions, and differentiating these from range expansions. Copyright © 2012 Elsevier Ltd. All rights reserved.
2011-09-09
Influenza A viruses are endemic in many animal species, including humans, swine, and wild birds, and sporadic cases of transmission of influenza A viruses between humans and animals do occur, including human infections with avian-origin influenza A viruses (i.e., H5N1 and H7N7) and swine-origin influenza A viruses (i.e., H1N1, H1N2, and H3N2). Genetic analysis can distinguish animal origin influenza viruses from the seasonal human influenza viruses that circulate widely and cause annual epidemics. This report describes two cases of febrile respiratory illness caused by swine-origin influenza A (H3N2) viruses identified on August 19 and August 26, 2011, and the current investigations. No epidemiologic link between the two cases has been identified, and although investigations are ongoing, no additional confirmed human infections with this virus have been detected. These viruses are similar to eight other swine-origin influenza A (H3N2) viruses identified from previous human infections over the past 2 years, but are unique in that one of the eight gene segments (matrix [M] gene) is from the 2009 influenza A (H1N1) virus. The acquisition of the M gene in these two swine-origin influenza A (H3N2) viruses indicates that they are "reassortants" because they contain genes of the swine-origin influenza A (H3N2) virus circulating in North American pigs since 1998 and the 2009 influenza A (H1N1) virus that might have been transmitted to pigs from humans during the 2009 H1N1 pandemic. However, reassortments of the 2009 influenza A (H1N1) virus with other swine influenza A viruses have been reported previously in swine. Clinicians who suspect influenza virus infection in humans with recent exposure to swine should obtain a nasopharyngeal swab from the patient for timely diagnosis at a state public health laboratory and consider empiric neuraminidase inhibitor antiviral treatment to quickly limit potential human transmission.
The aggregate complexity of decisions in the game of Go
NASA Astrophysics Data System (ADS)
Harré, M. S.; Bossomaier, T.; Gillett, A.; Snyder, A.
2011-04-01
Artificial intelligence (AI) research is fast approaching, or perhaps has already reached, a bottleneck whereby further advancement towards practical human-like reasoning in complex tasks needs further quantified input from large studies of human decision-making. Previous studies in psychology, for example, often rely on relatively small cohorts and very specific tasks. These studies have strongly influenced some of the core notions in AI research such as the reinforcement learning and the exploration versus exploitation paradigms. With the goal of contributing to this direction in AI developments we present our findings on the evolution towards world-class decision-making across large cohorts of subjects in the formidable game of Go. Some of these findings directly support previous work on how experts develop their skills but we also report on several previously unknown aspects of the development of expertise that suggests new avenues for AI research to explore. In particular, at the level of play that has so far eluded current AI systems for Go, we are able to quantify the lack of `predictability' of experts and how this changes with their level of skill.
Korchazhkina, Olga; Yang, Ying
2004-07-05
A previously described method of measurement of malondialdehyde (MDA) in human urine after derivatisation with 2,4-dinitrophenylhydrazine (DNPH) was tested for a possibility of using methyl malondialdehyde (MeMDA) as an internal standard. Despite structural similarity, those compounds were found to produce different yields of derivatisation under the same conditions depending on urine matrix. We conclude, that MeMDA is not suitable as an internal standard for the measurement of MDA in urine under previously reported conditions when DNPH is used as a deriviatising agent.
Sharmin, Sazia; Taguchi, Atsuhiro; Kaku, Yusuke; Yoshimura, Yasuhiro; Ohmori, Tomoko; Sakuma, Tetsushi; Mukoyama, Masashi; Yamamoto, Takashi; Kurihara, Hidetake; Nishinakamura, Ryuichi
2016-06-01
Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator-like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm-like structures. Microarray analysis of sorted iPS cell-derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell-derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell-derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases. Copyright © 2016 by the American Society of Nephrology.
Sharmin, Sazia; Taguchi, Atsuhiro; Kaku, Yusuke; Yoshimura, Yasuhiro; Ohmori, Tomoko; Sakuma, Tetsushi; Mukoyama, Masashi; Yamamoto, Takashi; Kurihara, Hidetake
2016-01-01
Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro. These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm–like structures. Microarray analysis of sorted iPS cell–derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo. Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell–derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell–derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases. PMID:26586691
Human genetic factors in tuberculosis: an update.
van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G
2017-09-01
Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.
Comments on human eurytremiasis in Brazil
Pinto, Hudson Alves; de Melo, Alan Lane
2016-01-01
Eurytremiasis is an important parasitic disease of cattle that was recently suggested to be a neglected and emerging human disease in Brazil. Based on a misinterpretation of the life cycle of the parasite, it was suggested that a great number of people could be infected with this fluke in the country. In the present letter, aspects of the life cycle of Eurytrema spp. are revisited and clarified. The mechanism of transmission previously reported for the few accidental human cases involved the ingestion of raw or undercooked insects (grasshoppers and crickets) harboring the infective metacercariae. In reality, the zoonotic potential of Eurytrema species is extremely low, and human eurytremiasis is not, and probably never will be, a zoonotic disease in countries where entomophagy is not a common food habit. PMID:27226956
Konishi, Yuko; Karnan, Sivasundaram; Takahashi, Miyuki; Ota, Akinobu; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki
2012-09-01
Gene targeting in a broad range of human somatic cell lines has been hampered by inefficient homologous recombination. To improve this technology and facilitate its widespread application, it is critical to first have a robust and efficient research system for measuring gene targeting efficiency. Here, using a fusion gene consisting of hygromycin B phosphotransferase and 3'-truncated enhanced GFP (HygR-5' EGFP) as a reporter gene, we created a molecular system monitoring the ratio of homologous to random integration (H/R ratio) of targeting vectors into the genome. Cell clones transduced with a reporter vector containing HygR-5' EGFP were efficiently established from two human somatic cell lines. Established HygR-5' EGFP reporter clones retained their capacity to monitor gene targeting efficiency for a longer duration than a conventional reporter system using an unfused 5' EGFP gene. With the HygR-5' EGFP reporter system, we reproduced previous findings of gene targeting frequency being up-regulated by the use of an adeno-associated viral (AAV) backbone, a promoter-trap system, or a longer homology arm in a targeting vector, suggesting that this system accurately monitors H/R ratio. Thus, our HygR-5' EGFP reporter system will assist in the development of an efficient AAV-based gene targeting technology.
Suzuki, Mika; Sato, Keiko
2016-07-01
Research Ethics Committees (RECs) are designed to protect human subjects in research. It is essential to recognize whether the RECs are achieving this goal. Several studies have reported on RECs; however, detailed data regarding the quality of research protocols and the review process of RECs have not been reported in Japan. We examine research protocols reviewed by RECs and the review processes at three institutions using a novel checklist we developed. The data show that approximately half of all examined protocols lacked a clearly written "Background" section that defines the study rationale and design. These results reiterate suggestions made in previous research regarding educational programs and support departments that could enhance responsible conduct in clinical research to protect human subjects in Japan. © The Author(s) 2016.
Sengul, Hatice; Santella, Nicholas; Steinberg, Laura J; Chermak, Christina
2010-09-01
To investigate the circumstances and geographic and temporal distributions of hazardous material releases and resulting human impacts in the United States. Releases with fatalities, injuries, and evacuations were identified from reports to the National Response Center between 1990 and 2008, correcting for data quality issues identified in previous studies. From more than 550,000 reports, 861 deaths, 16,348 injuries and 741,427 evacuations were identified. Injuries from releases of chemicals at fixed facilities and natural gas from pipelines have decreased whereas evacuations from petroleum releases at fixed facilities have increased. Results confirm recent advances in chemical and pipeline safety and suggest directions for further improvement including targeted training and inspections and adoption of inherently safer design principles.
A rare cause of acute flaccid paralysis: Human coronaviruses
Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S. Paksu; Haydar, A. Tasdemir
2015-01-01
Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian–Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time. PMID:26557177
A rare cause of acute flaccid paralysis: Human coronaviruses.
Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S Paksu; Haydar, A Tasdemir
2015-01-01
Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mann, J.M.; Francis, H.; Quinn, T.C.
1986-12-12
A study of seroprevalence of the human immunodeficiency virus involving 2384 (96%) of Mama Yemo Hospital's (Kinshasa, Zaire) 2492 personnel found 152 (6.4%) to be seropositive. Prevalence was higher among women than among men (8.1% vs 5.2%); in women peak seroprevalence (13.9%) occurred in 20 to 29-year-olds. Workers most likely to be seropositive were those who were relatively young, those who were unmarried, those reporting a blood transfusion or hospitalization during the previous ten years, and those receiving medical injections during the previous three years. Medical, administrative, and manual workers had similar seroprevalence (6.5%, 6.4%, and 6.0%, respectively), and seropositivitymore » was not associated with any measure of patient, blood, or needle contact. These findings are consistent with other hospital-based studies indicating low risks for occupational transmission of human immunodeficiency virus.« less
Mechanical property studies of human gallstones.
Stranne, S K; Cocks, F H; Gettliffe, R
1990-08-01
The recent development of gallstone fragmentation methods has increased the significance of the study of the mechanical properties of human gallstones. In the present work, fracture strength data and microhardness values of gallstones of various chemical compositions are presented as tested in both dry and simulated bile environments. Generally, both gallstone hardness and fracture strength values were significantly less than kidney stone values found in previous studies. However, a single calcium carbonate stone was found to have an outer shell hardness exceeding those values found for kidney stones. Diametral compression measurements in simulated bile conclusively demonstrated low gallstone fracture strength as well as brittle fracture in the stones tested. Based on the results of this study, one may conclude that the wide range of gallstone microhardnesses found may explain the reported difficulties previous investigators have experienced using various fragmentation techniques on specific gallstones. Moreover, gallstone mechanical properties may be relatively sensitive to bile-environment composition.
Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.
Forslund, Kristoffer; Hildebrand, Falk; Nielsen, Trine; Falony, Gwen; Le Chatelier, Emmanuelle; Sunagawa, Shinichi; Prifti, Edi; Vieira-Silva, Sara; Gudmundsdottir, Valborg; Pedersen, Helle K; Arumugam, Manimozhiyan; Kristiansen, Karsten; Voigt, Anita Yvonne; Vestergaard, Henrik; Hercog, Rajna; Costea, Paul Igor; Kultima, Jens Roat; Li, Junhua; Jørgensen, Torben; Levenez, Florence; Dore, Joël; Nielsen, H Bjørn; Brunak, Søren; Raes, Jeroen; Hansen, Torben; Wang, Jun; Ehrlich, S Dusko; Bork, Peer; Pedersen, Oluf
2015-12-10
In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.
ERIC Educational Resources Information Center
van der Wel, Robrecht P. R. D.; Fleckenstein, Robin M.; Jax, Steven A.; Rosenbaum, David A.
2007-01-01
Previous research suggests that motor equivalence is achieved through reliance on effector-independent spatiotemporal forms. Here the authors report a series of experiments investigating the role of such forms in the production of movement sequences. Participants were asked to complete series of arm movements in time with a metronome and, on some…
Frawley, Alean; Powell, Lauren; McQuiston, John R; Gulvik, Christopher A; Bégué, Rodolfo E
2018-04-23
Chromobacterium violaceum is a rare, potentially serious pathogen. Most clinicians have no experience with its clinical appearance or treatment. We describe a case of a child presenting with necrotizing pneumonia caused by C. violaceum . We describe case complexities, including the need for a multidisciplinary approach to diagnosis and treatment.
John G. Hof; Curtis H. Flather; Tony J. Baltic; Rudy M. King
2004-01-01
This article reports the methodology and results of a data envelopment analysis (DEA) that attempts to identify areas in the country where there is maximum potential for improving the forest and rangeland condition, based on 12 indicator variables. This analysis differs from previous DEA studies in that the primary variables are measures of human activity and...
ERIC Educational Resources Information Center
Ntombela, Sithabile
2013-01-01
The South African Constitution upholds and entrenches the human right of all citizens. Similarly, the Higher Education Act of 1997 promotes equality of access for all, especially for those previously marginalised or excluded. The study reported in this article explored challenges experienced by students with disabilities at his university. Using…
USDA-ARS?s Scientific Manuscript database
Our previous study suggested that javamide-II found in coffee could inhibit sirtuin1/2, thereby potentially beneficial in some human diseases such as neuronal degenerative diseases and cancer. In fact, coffee is reported to contain javamide-I, in addition to javamide-II. However, potential effects o...
Reynolds, Conner D.; Jefferson, Taylor S.; Volquardsen, Meagan; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Lugo, Joaquin N.
2017-01-01
Background: The piracetam analog, aniracetam, has recently received attention for its cognition enhancing potential, with minimal reported side effects. Previous studies report the drug to be effective in both human and non-human models with pre-existing cognitive dysfunction, but few studies have evaluated its efficacy in healthy subjects. A previous study performed in our laboratory found no cognitive enhancing effects of oral aniracetam administration 1-hour prior to behavioral testing in naïve C57BL/6J mice. Methods: The current study aims to further evaluate this drug by administration of aniracetam 30 minutes prior to testing in order to optimize any cognitive enhancing effects. In this study, all naïve C57BL/6J mice were tested in tasks of delayed fear conditioning, novel object recognition, rotarod, open field, elevated plus maze, and marble burying. Results: Across all tasks, animals in the treatment group failed to show enhanced learning when compared to controls. Conclusions: These results provide further evidence suggesting that aniracetam conveys no therapeutic benefit to subjects without pre-existing cognitive dysfunction. PMID:29946420
Johnstone, A M
2007-05-01
Adult humans often undertake acute fasts for cosmetic, religious or medical reasons. For example, an estimated 14% of US adults have reported using fasting as a means to control body weight and this approach has long been advocated as an intermittent treatment for gross refractory obesity. There are unique historical data sets on extreme forms of food restriction that give insight into the consequences of starvation or semi-starvation in previously healthy, but usually non-obese subjects. These include documented medical reports on victims of hunger strike, famine and prisoners of war. Such data provide a detailed account on how the body adapts to prolonged starvation. It has previously been shown that fasting for the biblical period of 40 days and 40 nights is well within the overall physiological capabilities of a healthy adult. However, the specific effects on the human body and mind are less clearly documented, either in the short term (hours) or in the longer term (days). This review asks the following three questions, pertinent to any weight-loss therapy, (i) how effective is the regime in achieving weight loss, (ii) what impact does it have on psychology? and finally, (iii) does it work long-term?
Avian Schistosomes and Outbreaks of Cercarial Dermatitis
Mikeš, Libor; Lichtenbergová, Lucie; Skála, Vladimír; Soldánová, Miroslava; Brant, Sara Vanessa
2015-01-01
SUMMARY Cercarial dermatitis (swimmer's itch) is a condition caused by infective larvae (cercariae) of a species-rich group of mammalian and avian schistosomes. Over the last decade, it has been reported in areas that previously had few or no cases of dermatitis and is thus considered an emerging disease. It is obvious that avian schistosomes are responsible for the majority of reported dermatitis outbreaks around the world, and thus they are the primary focus of this review. Although they infect humans, they do not mature and usually die in the skin. Experimental infections of avian schistosomes in mice show that in previously exposed hosts, there is a strong skin immune reaction that kills the schistosome. However, penetration of larvae into naive mice can result in temporary migration from the skin. This is of particular interest because the worms are able to migrate to different organs, for example, the lungs in the case of visceral schistosomes and the central nervous system in the case of nasal schistosomes. The risk of such migration and accompanying disorders needs to be clarified for humans and animals of interest (e.g., dogs). Herein we compiled the most comprehensive review of the diversity, immunology, and epidemiology of avian schistosomes causing cercarial dermatitis. PMID:25567226
NASA Astrophysics Data System (ADS)
Henneberg, Maciej; Eckhardt, Robert B.; Chavanaves, Sakdapong; Hsü, Kenneth J.
2014-08-01
Human skeletons from Liang Bua Cave, Flores, Indonesia, are coeval with only Homo sapiens populations worldwide and no other previously known hominins. We report here for the first time to our knowledge the occipitofrontal circumference of specimen LB1. This datum makes it possible to link the 430-mL endocranial volume of LB1 reported by us previously, later confirmed independently by other investigators, not only with other human skeletal samples past and present but also with a large body of clinical data routinely collected on patients with developmental disorders. Our analyses show that the brain size of LB1 is in the range predicted for an individual with Down syndrome (DS) in a normal small-bodied population from the geographic region that includes Flores. Among additional diagnostic signs of DS and other skeletal dysplasiae are abnormally short femora combined with disproportionate flat feet. Liang Bua Cave femora, known only for LB1, match interlimb proportions for DS. Predictions based on corrected LB1 femur lengths show a stature normal for other H. sapiens populations in the region.
Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.
Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B
2003-05-01
Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.
Piseddu, E; Trotta, M; Tortoli, E; Avanzi, M; Tasca, S; Solano-Gallego, L
2011-01-01
Mycobacterium celatum is a slow growing non-tuberculous mycobacterium described mainly as occurring in human patients. Only two cases of infection with this pathogen have been reported previously in animals. A 5-year-old, neutered male ferret was presented with progressive weight loss and muscle atrophy. Pale mucous membranes, slight alopecia of the tail and splenomegaly, confirmed by abdominal ultrasound, were observed. Fine-needle aspirations of the spleen revealed extramedullary haematopoiesis and marked macrophage-dominated inflammation associated with mycobacterial infection. Ziehl-Neelsen staining demonstrated sporadic acid-fast bacilli within macrophages. These organisms were identified as M. celatum by microbiological and molecular methods. Phylogenetic analysis based on the 16S rDNA gene compared this isolate with previously reported strains and demonstrated close relatedness to the human strains of M. celatum types 1 and 3. The ferret was treated with enrofloxacin, rifampicin and azithromycin, resulting in clinical improvement. After 40 days of treatment, the spleen was re-evaluated. Cytological evaluation revealed only extramedullary haematopoiesis without evidence of infection. Discontinuation of therapy was followed by rapid deterioration and death. Copyright © 2010 Elsevier Ltd. All rights reserved.
Functional correlates of the anterolateral processing hierarchy in human auditory cortex.
Chevillet, Mark; Riesenhuber, Maximilian; Rauschecker, Josef P
2011-06-22
Converging evidence supports the hypothesis that an anterolateral processing pathway mediates sound identification in auditory cortex, analogous to the role of the ventral cortical pathway in visual object recognition. Studies in nonhuman primates have characterized the anterolateral auditory pathway as a processing hierarchy, composed of three anatomically and physiologically distinct initial stages: core, belt, and parabelt. In humans, potential homologs of these regions have been identified anatomically, but reliable and complete functional distinctions between them have yet to be established. Because the anatomical locations of these fields vary across subjects, investigations of potential homologs between monkeys and humans require these fields to be defined in single subjects. Using functional MRI, we presented three classes of sounds (tones, band-passed noise bursts, and conspecific vocalizations), equivalent to those used in previous monkey studies. In each individual subject, three regions showing functional similarities to macaque core, belt, and parabelt were readily identified. Furthermore, the relative sizes and locations of these regions were consistent with those reported in human anatomical studies. Our results demonstrate that the functional organization of the anterolateral processing pathway in humans is largely consistent with that of nonhuman primates. Because our scanning sessions last only 15 min/subject, they can be run in conjunction with other scans. This will enable future studies to characterize functional modules in human auditory cortex at a level of detail previously possible only in visual cortex. Furthermore, the approach of using identical schemes in both humans and monkeys will aid with establishing potential homologies between them.
ISOFORMS OF VITAMIN E DIFFERENTIALLY REGULATE INFLAMMATION
Cook-Mills, Joan M.; McCary, Christine A.
2011-01-01
Vitamin E regulation of disease has been extensively studied in humans, animal models and cell systems. Most of these studies focus on the α-tocopherol isoform of vitamin E. These reports indicate contradictory outcomes for anti-inflammatory functions of the α-tocopherol isoform of vitamin E, especially with regards to clinical studies of asthma and atherosclerosis. These seemingly disparate clinical results are consistent with recently reported unrecognized properties of isoforms of vitamin E. Recently, it has been reported that physiological levels of purified natural forms of vitamin E have opposing regulatory functions during inflammation. These opposing regulatory functions by physiological levels of vitamin E isoforms impact interpretations of previous studies on vitamin E. Moreover, additional recent studies also indicate that the effects of vitamin E isoforms on inflammation are only partially reversible using physiological levels of a vitamin E isoform with opposing immunoregulatory function. Thus, this further influences interpretations of previous studies with vitamin E in which there was inflammation and substantial vitamin E isoforms present before the initiation of the study. In summary, this review will discuss regulation of inflammation by vitamin E, including alternative interpretations of previous studies in the literature with regards to vitamin E isoforms. PMID:20923401
Oyarzún, Javiera P; Packard, Pau A; de Diego-Balaguer, Ruth; Fuentemilla, Lluis
2016-09-01
Neurobiological models of long-term memory explain how memory for inconsequential events fades, unless these happen before or after other relevant (i.e., rewarding or aversive) or novel events. Recently, it has been shown in humans that retrospective and prospective memories are selectively enhanced if semantically related events are paired with aversive stimuli. However, it remains unclear whether motivating stimuli, as opposed to aversive, have the same effect in humans. Here, participants performed a three phase incidental encoding task where one semantic category was rewarded during the second phase. A memory test 24h after, but not immediately after encoding, revealed that memory for inconsequential items was selectively enhanced only if items from the same category had been previously, but not subsequently, paired with rewards. This result suggests that prospective memory enhancement of reward-related information requires, like previously reported for aversive memories, of a period of memory consolidation. The current findings provide the first empirical evidence in humans that the effects of motivated encoding are selectively and prospectively prolonged over time. Copyright © 2016 Elsevier Inc. All rights reserved.
A draft annotation and overview of the human genome
Wright, Fred A; Lemon, William J; Zhao, Wei D; Sears, Russell; Zhuo, Degen; Wang, Jian-Ping; Yang, Hee-Yung; Baer, Troy; Stredney, Don; Spitzner, Joe; Stutz, Al; Krahe, Ralf; Yuan, Bo
2001-01-01
Background The recent draft assembly of the human genome provides a unified basis for describing genomic structure and function. The draft is sufficiently accurate to provide useful annotation, enabling direct observations of previously inferred biological phenomena. Results We report here a functionally annotated human gene index placed directly on the genome. The index is based on the integration of public transcript, protein, and mapping information, supplemented with computational prediction. We describe numerous global features of the genome and examine the relationship of various genetic maps with the assembly. In addition, initial sequence analysis reveals highly ordered chromosomal landscapes associated with paralogous gene clusters and distinct functional compartments. Finally, these annotation data were synthesized to produce observations of gene density and number that accord well with historical estimates. Such a global approach had previously been described only for chromosomes 21 and 22, which together account for 2.2% of the genome. Conclusions We estimate that the genome contains 65,000-75,000 transcriptional units, with exon sequences comprising 4%. The creation of a comprehensive gene index requires the synthesis of all available computational and experimental evidence. PMID:11516338
Panning, B; Smiley, J R
1993-01-01
We found that transcription of endogenous human Alu elements by RNA polymerase III was strongly stimulated following infection of HeLa cells with adenovirus type 5, leading to the accumulation of high levels of Alu transcripts initiated from Alu polymerase III promoters. In contrast to previously reported cases of adenovirus-induced activation of polymerase III transcription, induction required the E1b 58-kDa protein and the products of E4 open reading frames 3 and 6 in addition to the 289-residue E1a protein. In addition, E1a function was not required at high multiplicities of infection, suggesting that E1a plays an indirect role in Alu activation. These results suggest previously unsuspected regulatory properties of the adenovirus E1b and E4 gene products and provide a novel approach to the study of the biology of the most abundant class of dispersed repetitive DNA in the human genome. Images PMID:7684492
Dynamic Modulation of Human Motor Activity When Observing Actions
Press, Clare; Cook, Jennifer; Blakemore, Sarah-Jayne; Kilner, James
2012-01-01
Previous studies have demonstrated that when we observe somebody else executing an action many areas of our own motor systems are active. It has been argued that these motor activations are evidence that we motorically simulate observed actions; this motoric simulation may support various functions such as imitation and action understanding. However, whether motoric simulation is indeed the function of motor activations during action observation is controversial, due to inconsistency in findings. Previous studies have demonstrated dynamic modulations in motor activity when we execute actions. Therefore, if we do motorically simulate observed actions, our motor systems should also be modulated dynamically, and in a corresponding fashion, during action observation. Using magnetoencephalography, we recorded the cortical activity of human participants while they observed actions performed by another person. Here, we show that activity in the human motor system is indeed modulated dynamically during action observation. The finding that activity in the motor system is modulated dynamically when observing actions can explain why studies of action observation using functional magnetic resonance imaging have reported conflicting results, and is consistent with the hypothesis that we motorically simulate observed actions. PMID:21414901
Montgomery, Joel M.; Blair, Patrick J.; Carroll, Darin S.; Mills, James N.; Gianella, Alberto; Iihoshi, Naomi; Briggiler, Ana M.; Felices, Vidal; Salazar, Milagros; Olson, James G.; Glabman, Raisa A.; Bausch, Daniel G.
2012-01-01
We report the results of an investigation of a small outbreak of hantavirus pulmonary syndrome in 2002 in the Department of Santa Cruz, Bolivia, where the disease had not previously been reported. Two cases were initially reported. The first case was a physician infected with Laguna Negra virus during a weekend visit to his ranch. Four other persons living on the ranch were IgM antibody-positive, two of whom were symptomatic for mild hantavirus pulmonary syndrome. The second case was a migrant sugarcane worker. Although no sample remained to determine the specific infecting hantavirus, a virus 90% homologous with Río Mamoré virus was previously found in small-eared pygmy rice rats (Oligoryzomys microtis) trapped in the area. An antibody prevalence study conducted in the region as part of the outbreak investigation showed 45 (9.1%) of 494 persons to be IgG positive, illustrating that hantavirus infection is common in Santa Cruz Department. Precipitation in the months preceding the outbreak was particularly heavy in comparison to other years, suggesting a possible climatic or ecological influence on rodent populations and risk of hantavirus transmission to humans. Hantavirus infection appears to be common in the Santa Cruz Department, but more comprehensive surveillance and field studies are needed to fully understand the epidemiology and risk to humans. PMID:23094116
Heyne, Kristina; Kölsch, Kathrin; Bruand, Marine; Kremmer, Elisabeth; Grässer, Friedrich A; Mayer, Jens; Roemer, Klaus
2015-01-01
Humans and primates are long-lived animals with long reproductive phases. One factor that appears to contribute to longevity and fertility in humans, as well as to cancer-free survival, is the transcription factor and tumor suppressor p53, controlled by its main negative regulator MDM2. However, p53 and MDM2 homologs are found throughout the metazoan kingdom from Trichoplacidae to Hominidae. Therefore the question arises, if p53/MDM2 contributes to the shaping of primate features, then through which mechanisms. Previous findings have indicated that the appearances of novel p53-regulated genes and wild-type p53 variants during primate evolution are important in this context. Here, we report on another mechanism of potential relevance. Human endogenous retrovirus K subgroup HML-2 (HERV-K(HML-2)) type 1 proviral sequences were formed in the genomes of the predecessors of contemporary Hominoidea and can be identified in the genomes of Nomascus leucogenys (gibbon) up to Homo sapiens. We previously reported on an alternative splicing event in HERV-K(HML-2) type 1 proviruses that can give rise to nuclear protein of 9 kDa (Np9). We document here the evolution of Np9-coding capacity in human, chimpanzee and gorilla, and show that the C-terminal half of Np9 binds directly to MDM2, through a domain of MDM2 that is known to be contacted by various cellular proteins in response to stress. Np9 can inhibit the MDM2 ubiquitin ligase activity toward p53 in the cell nucleus, and can support the transactivation of genes by p53. Our findings point to the possibility that endogenous retrovirus protein Np9 contributes to the regulation of the p53-MDM2 pathway specifically in humans, chimpanzees and gorillas. PMID:26103464
Gonococcal arthritis in human immunodeficiency virus-infected patients. Review of the literature.
Sena Corrales, Gabriel; Mora Navas, Laura; Palacios Muñoz, Rosario; García López, Victoria; Márquez Solero, Manuel; Santos González, Jesús
We report a case of gonococcal arthritis in a patient with human immunodeficiency virus (HIV) infection and review 17 previously published cases; only one patient presented urethritis, and blood cultures were positive in one case. Gonococcal arthritis is rare in HIV-infected patients and is not usually associated with other symptoms. It should be considered in the differential diagnosis of acute arthritis in patients with HIV infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Molecular Toxicology of Chromatin: The Role of Poly(ADP-Ribose) in Gene Control.
1985-02-01
04 4 0V 0 r4. $) 4 0n U) Ln V W 0 Ř (u %D -T -a Ai j4 W0 .. 04 04 0 04rd 412% I cb 01 41 410 41 .j A . . to 2.4 Ř -A 411 0 2 0 -r 0. 04 0A CAt e4...reported previously (1). The selection procedures used for NNSF * were compared with fibrosarcoma . Ieionmyosarcoui and synovial sarcoma cells. V...tumor incidence of human fibrosarcoma , lelomyosarcoma and synovial sarcoma cells in nude mice was identical with that of UV-transformed human
2013-03-26
virus (IIV) vaccine (dose 0.5 mL intramuscularly, purchased in Thailand from Sanofi Pasteur). Both vaccines contained the three strains for the 2009/10...H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial. 5a. CONTRACT NUMBER...reported by WHO since 2003 [1]. Current seasonal trivalent influenza vaccines rely on predicted antigens based on the previous season’s circulating
Hassan, Md. Imtaiyaz; Waheed, Abdul; Grubb, Jeffery H.; Klei, Herbert E.; Korolev, Sergey; Sly, William S.
2013-01-01
Human β-glucuronidase (GUS) cleaves β-D-glucuronic acid residues from the non-reducing termini of glycosaminoglycan and its deficiency leads to mucopolysaccharidosis type VII (MPSVII). Here we report a high resolution crystal structure of human GUS at 1.7 Å resolution and present an extensive analysis of the structural features, unifying recent findings in the field of lysosome targeting and glycosyl hydrolases. The structure revealed several new details including a new glycan chain at Asn272, in addition to that previously observed at Asn173, and coordination of the glycan chain at Asn173 with Lys197 of the lysosomal targeting motif which is essential for phosphotransferase recognition. Analysis of the high resolution structure not only provided new insights into the structural basis for lysosomal targeting but showed significant differences between human GUS, which is medically important in its own right, and E. coli GUS, which can be selectively inhibited in the human gut to prevent prodrug activation and is also widely used as a reporter gene by plant biologists. Despite these differences, both human and E. coli GUS share a high structure homology in all three domains with most of the glycosyl hydrolases, suggesting that they all evolved from a common ancestral gene. PMID:24260279
Gledhill, Karl; Guo, Zongyou; Umegaki-Arao, Noriko; Higgins, Claire A; Itoh, Munenari; Christiano, Angela M
2015-01-01
The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.
Preferred gait and walk-run transition speeds in ostriches measured using GPS-IMU sensors.
Daley, Monica A; Channon, Anthony J; Nolan, Grant S; Hall, Jade
2016-10-15
The ostrich (Struthio camelus) is widely appreciated as a fast and agile bipedal athlete, and is a useful comparative bipedal model for human locomotion. Here, we used GPS-IMU sensors to measure naturally selected gait dynamics of ostriches roaming freely over a wide range of speeds in an open field and developed a quantitative method for distinguishing walking and running using accelerometry. We compared freely selected gait-speed distributions with previous laboratory measures of gait dynamics and energetics. We also measured the walk-run and run-walk transition speeds and compared them with those reported for humans. We found that ostriches prefer to walk remarkably slowly, with a narrow walking speed distribution consistent with minimizing cost of transport (CoT) according to a rigid-legged walking model. The dimensionless speeds of the walk-run and run-walk transitions are slower than those observed in humans. Unlike humans, ostriches transition to a run well below the mechanical limit necessitating an aerial phase, as predicted by a compass-gait walking model. When running, ostriches use a broad speed distribution, consistent with previous observations that ostriches are relatively economical runners and have a flat curve for CoT against speed. In contrast, horses exhibit U-shaped curves for CoT against speed, with a narrow speed range within each gait for minimizing CoT. Overall, the gait dynamics of ostriches moving freely over natural terrain are consistent with previous lab-based measures of locomotion. Nonetheless, ostriches, like humans, exhibit a gait-transition hysteresis that is not explained by steady-state locomotor dynamics and energetics. Further study is required to understand the dynamics of gait transitions. © 2016. Published by The Company of Biologists Ltd.
de Llanos, Rosa; Querol, Amparo; Pemán, Javier; Gobernado, Miguel; Fernández-Espinar, María Teresa
2006-08-01
We report four cases of blood cultures testing positive for yeast strains belonging to the species Saccharomyces cerevisiae. Using molecular techniques, RFLP of mtDNA and delta-PCR amplification, we show the association of two of the isolates with non-clinical strains. Specifically, with two commercial bread-making strains and the therapeutic S. boulardii strain. The association of S. boulardii with cases of fungemia has been reported previously. Nevertheless, this is the first time that a baker's yeast has been isolated from blood.
Thakur, B K; Verma, S; Mishra, J
2015-06-01
Human immunodeficiency virus-infected patients are at increased risk of drug reactions because of immune dysregulation and multiple drug intake. Lichenoid drug reactions to isoniazid have been reported previously in the literature. However, for lichenoid drug reaction to isoniazid to be so extensive to present as exfoliative dermatitis is rare. We report here a rare case of lichenoid drug reaction to isoniazid presenting as exfoliative dermatitis in a patient with acquired immunodeficiency syndrome. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China.
Ke, Changwen; Mok, Chris Ka Pun; Zhu, Wenfei; Zhou, Haibo; He, Jianfeng; Guan, Wenda; Wu, Jie; Song, Wenjun; Wang, Dayan; Liu, Jiexiong; Lin, Qinhan; Chu, Daniel Ka Wing; Yang, Lei; Zhong, Nanshan; Yang, Zifeng; Shu, Yuelong; Peiris, Joseph Sriyal Malik
2017-07-01
The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient's adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.
Effect of the GPI anchor of human Thy-1 on antibody recognition and function
Bradley, John E.; Chan, Joy M.; Hagood, James S.
2012-01-01
Thymocyte differentiation antigen 1 (Thy-1) is a glycosylphosphatidyl inositol (GPI)-linked cell surface glycoprotein expressed on numerous cell types, which regulates signals affecting cell adhesion, migration, differentiation, and survival. In addition, Thy-1 has been detected in serum, cerebral spinal fluid, wound fluid from venous ulcers, synovial fluid from joints in rheumatoid arthritis and more recently urine. We previously detected Thy-1 in the conditioned media of cytokine-stimulated lung fibroblasts, suggesting that Thy-1 shedding may be a response to cellular stress. Soluble and membrane bound forms of Thy-1 from in vivo sources have been shown to be identical in size when deglycosylated, suggesting that soluble Thy-1 is separated from the diacyl glycerol portion of its GPI-anchor by hydrolysis within the GPI moiety. For Thy-1 and other GPI-anchored proteins, delipidation induces a stable change in conformation that manifests itself in a change in antibody affinity for soluble forms. Using epitope tagged recombinant soluble Thy-1, we report that widely available monoclonal antibodies to human Thy-1 are unable to detect soluble Thy-1 by immunoblotting. We reevaluated the Thy-1 that we previously reported in the conditioned media of normal human lung fibroblasts and found it to be entirely insoluble. These findings suggest that most Thy-1 reported in body fluids retains its GPI anchor and may be associated with membrane fragments or vesicles. This phenomenon should be considered in the generation of antibodies and controls for Thy-1 bioassays. Furthermore, the changes in Thy-1 conformation with delipidation, beyond affecting antibody affinity, likely affect the ligand affinity and biological function of soluble vs. released membrane-associated forms. PMID:23358110
Zeng, Zhaolin; Zhao, Wei; Liu, Aiqin; Piao, Daxun; Jiang, Tao; Cao, Jianping; Shen, Yujuan; Liu, Hua; Zhang, Weizhe
2014-01-01
Cystic echinococcosis (CE) caused by the larval stage of Echinococcus granulosus sensu lato (s.l.) is one of the most important zoonotic parasitic diseases worldwide and 10 genotypes (G1–G10) have been reported. In China, almost all the epidemiological and genotyping studies of E. granulosus s.l. are from the west and northwest pasturing areas. However, in Heilongjiang Province of northeastern China, no molecular information is available on E. granulosus s.l. To understand and to speculate on possible transmission patterns of E. granulosus s.l., we molecularly identified and genotyped 10 hydatid cysts from hepatic CE patients in Heilongjiang Province based on mitochondrial cytochrome c oxidase subunit I (cox1), cytochrome b (cytb) and NADH dehydrogenase subunit 1 (nad1) genes. Two genotypes were identified, G1 genotype (n = 6) and G7 genotype (n = 4). All the six G1 genotype isolates were identical to each other at the cox1 locus; three and two different sequences were obtained at the cytb and nad1 loci, respectively, with two cytb gene sequences not being described previously. G7 genotype isolates were identical to each other at the cox1, cytb and nad1 loci; however, the cytb gene sequence was not described previously. This is the first report of G7 genotype in humans in China. Three new cytb gene sequences from G1 and G7 genotypes might reflect endemic genetic characterizations. Pigs might be the main intermediate hosts of G7 genotype in our investigated area by homology analysis. The results will aid in making more effective control strategies for the prevention of transmission of E. granulosus s.l. PMID:25329820
The human gut microbiota and virome: Potential therapeutic implications.
Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio
2015-12-01
Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Identification of a µ opiate receptor signaling mechanism in human placenta.
Mantione, Kirk J; Angert, Robert M; Cadet, Patrick; Kream, Richard M; Stefano, George B
2010-11-01
Previous studies report that genes in the morphine biosynthetic pathway have been found in placental tissue. Prior researchers have shown that kappa opioid receptors are present in human placenta. We determined if a µ opiate receptor was present and which subtype was expressed in human placenta. We also sought to demonstrate a functional µ opiate receptor in human placenta. Polymerase chain reactions as well as DNA sequencing were performed to identify the µ opiate receptor subtypes present in human placenta. The functionality of the receptor was demonstrated by real time amperometric measurements of morphine induced NO release. The µ4 opiate receptor sequence was present as well as the µ1 opioid receptor transcript. The addition of morphine to placental tissue resulted in immediate nitric oxide release and this effect was blocked by naloxone. In the present study, an intact morphine signaling system has been demonstrated in human placenta. Morphine signaling in human placenta probably functions to regulate the immune, vascular, and endocrine functions of this organ via NO.
Identification of the Human SULT Enzymes Involved in the Metabolism of Rotigotine.
Jia, Chaojun; Luo, Lijun; Kurogi, Katsuhisa; Yu, Juming; Zhou, Chunyang; Liu, Ming-Cheh
2016-06-01
Sulfation has been reported to be a major pathway for the metabolism and inactivation of rotigotine in vivo. The current study aimed to identify the human cytosolic sulfotransferase (SULT) enzyme(s) capable of mediating the sulfation of rotigotine. Of the 13 known human SULTs examined, 6 of them (SULT1A1, 1A2, 1A3, 1B1, 1C4, 1E1) displayed significant sulfating activities toward rotigotine. pH dependence and kinetic parameters of the sulfation of rotigotine by relevant human SULTs were determined. Of the 6 human organ samples tested, small intestine and liver cytosols displayed considerably higher rotigotine-sulfating activity than did brain, lung, and kidney. Moreover, sulfation of rotigotine was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under metabolic conditions. Collectively, the results obtained provided a molecular basis underlying the previous finding of the excretion of sulfated rotigotine by patients undergoing treatment with rotigotine. © 2015, The American College of Clinical Pharmacology.
Alu repeat discovery and characterization within human genomes
Hormozdiari, Fereydoun; Alkan, Can; Ventura, Mario; Hajirasouliha, Iman; Malig, Maika; Hach, Faraz; Yorukoglu, Deniz; Dao, Phuong; Bakhshi, Marzieh; Sahinalp, S. Cenk; Eichler, Evan E.
2011-01-01
Human genomes are now being rapidly sequenced, but not all forms of genetic variation are routinely characterized. In this study, we focus on Alu retrotransposition events and seek to characterize differences in the pattern of mobile insertion between individuals based on the analysis of eight human genomes sequenced using next-generation sequencing. Applying a rapid read-pair analysis algorithm, we discover 4342 Alu insertions not found in the human reference genome and show that 98% of a selected subset (63/64) experimentally validate. Of these new insertions, 89% correspond to AluY elements, suggesting that they arose by retrotransposition. Eighty percent of the Alu insertions have not been previously reported and more novel events were detected in Africans when compared with non-African samples (76% vs. 69%). Using these data, we develop an experimental and computational screen to identify ancestry informative Alu retrotransposition events among different human populations. PMID:21131385
Rickettsia Species in Ticks Removed from Humans in Istanbul, Turkey
Gargili, Aysen; Palomar, Ana M.; Midilli, Kenan; Portillo, Aránzazu; Kar, Sırrı
2012-01-01
Abstract A total of 167 ticks collected from humans in Istanbul (Turkey) in 2006 were screened for Rickettsia species, and nested PCRs targeting gltA and ompA rickettsial fragment genes were carried out. Rickettsia monacensis (51), R. aeschlimannii (8), R. conorii subsp. conorii (3), R. helvetica (2), R. raoultii (1), R. africae (1), R. felis (1), and other Rickettsia spp. (2), were detected. To our knowledge, these Rickettsia species (except R. conorii) had never been reported in ticks removed from humans in Turkey. The presence of R. africae also had not been previously described, either in Hyalomma ticks or in any European tick species. In addition, R. aeschlimannii and R. felis had not been found associated with Rhipicephalus bursa specimens. The presence of human pathogenic Rickettsia in ticks removed from humans provides information about the risk of tick-borne rickettsioses in Turkey. PMID:22925016
Evidence for avian H9N2 influenza virus infections among rural villagers in Cambodia.
Blair, Patrick J; Putnam, Shannon D; Krueger, Whitney S; Chum, Channimol; Wierzba, Thomas F; Heil, Gary L; Yasuda, Chadwick Y; Williams, Maya; Kasper, Matthew R; Friary, John A; Capuano, Ana W; Saphonn, Vonthanak; Peiris, Malik; Shao, Hongxia; Perez, Daniel R; Gray, Gregory C
2013-04-01
Southeast Asia remains a critical region for the emergence of novel and/or zoonotic influenza, underscoring the importance of extensive sampling in rural areas where early transmission is most likely to occur. In 2008, 800 adult participants from eight sites were enrolled in a prospective population-based study of avian influenza (AI) virus transmission where highly pathogenic avian influenza (HPAI) H5N1 virus had been reported in humans and poultry from 2006 to 2008. From their enrollment sera and questionnaires, we report risk factor findings for serologic evidence of previous infection with 18 AI virus strains. Serologic assays revealed no evidence of previous infection with 13 different low-pathogenic AI viruses or with HPAI avian-like A/Cambodia/R0404050/2007(H5N1). However, 21 participants had elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2), validated with a monoclonal antibody blocking ELISA assay specific for avian H9. Although cross-reaction from antibodies against human influenza viruses cannot be completely excluded, the study data suggest that a number of participants were previously infected with the avian-like A/Hong Kong/1073/1999(H9N2) virus, likely due to as yet unidentified environmental exposures. Prospective data from this cohort will help us better understand the serology of zoonotic influenza infection in a rural cohort in SE Asia. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.
Septic arthritis due to Cellulosimicrobium cellulans.
Magro-Checa, César; Chaves-Chaparro, Lara; Parra-Ruiz, Jorge; Peña-Monje, Alejandro; Rosales-Alexander, José Luis; Salvatierra, Juan; Raya, Enrique
2011-12-01
Cellulosimicrobium cellulans has been reported as a rare cause of human pathogenesis. Infections mainly occur in immunocompromised patients and very often are associated with a foreign body. We report the first case of septic arthritis caused by C. cellulans in an immunocompetent patient. Our patient suffered a penetrating palm tree thorn injury to his left knee 8 weeks before admission. Although no foreign objects were found, they were suspected because previous reports suggest a frequent association with this microorganism, and open debridament was performed. Removal of foreign bodies related to this organism must be considered a high-priority treatment in these patients to achieve a complete recovery.
2018-01-01
Skin lesion which develops after deep sea diving is termed as coral dermatitis. The corals are known to produce a toxic substance which when comes in to contact with human skin may elicit hypersensitive reactions. Most previous reports highlight the allergic reactions caused by deep sea diving. This is a rare case of staphylococcal skin infection in a second-year medical student caused by Staphylococcus aureus; he reported a history of deep sea diving before being presented to the hospital with skin rashes. This case highlights the importance of considering infectious aetiology in cases of coral dermatitis. PMID:29666774
Carrió, Esperança; Rigat, Montse; Garnatje, Teresa; Mayans, Marina; Parada, Montse; Vallès, Joan
2012-01-01
This paper presents the results of an ethnobotanical study centred in veterinarian uses in two Catalan Pyrenean regions (Alt Empordà -AE- and High River Ter Valley -AT-, Iberian peninsula) and two Balearic Islands areas (Formentera -FO- and northeastern Mallorca -MA-). In the areas studied, 97 plant species have been claimed to be useful for veterinary purposes. A total of 306 veterinary use reports have been gathered and analysed. The ten most reported plants are Tanacetum parthenium (24 use reports), Parietaria officinalis (15), Ranunculus parnassifolius (14), Meum athamanticum (13), Olea europaea (13), Quercus ilex (12), Ruta chalepensis (12), Sambucus nigra (10) and Thymus vulgaris (10). According to comprehensive reviews, a high number of novelties for plant ethnoveterinary are contributed: 34 species and one subspecies, 11 genera, and three families have not been reported in previous works in this field, and 21 species had only been mentioned once. Several ethnoveterinary uses are coincidental with those in human medicine. Although ethnoveterinary practices are less relevant than in the past in the territories considered, as in all industrialised countries, the knowledge on plant properties and applications is still rich and constitutes a large pool of evidence for phytotherapy, both in domestic animals and humans. PMID:22829861
Corridors of migrating neurons in the human brain and their decline during infancy.
Sanai, Nader; Nguyen, Thuhien; Ihrie, Rebecca A; Mirzadeh, Zaman; Tsai, Hui-Hsin; Wong, Michael; Gupta, Nalin; Berger, Mitchel S; Huang, Eric; Garcia-Verdugo, Jose-Manuel; Rowitch, David H; Alvarez-Buylla, Arturo
2011-09-28
The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes. Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans. In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports, this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb--we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates.
Tamada, Taro; Honjo, Eijiro; Maeda, Yoshitake; Okamoto, Tomoyuki; Ishibashi, Matsujiro; Tokunaga, Masao; Kuroki, Ryota
2006-01-01
A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 Å resolution. The GCSF:GCSF-R complex formed a 2:2 stoichiometry by means of a cross-over interaction between the Ig-like domains of GCSF-R and GCSF. The conformation of the complex is quite different from that between human GCSF and the cytokine receptor homologous domain of mouse GCSF-R, but similar to that of the IL-6/gp130 signaling complex. The Ig-like domain cross-over structure necessary for GCSF-R activation is consistent with previously reported thermodynamic and mutational analyses. PMID:16492764
Chemical Analysis of Exhaled Human Breath Using High Resolution Mm-Wave Rotational Spectra
NASA Astrophysics Data System (ADS)
Guo, Tianle; Branco, Daniela; Thomas, Jessica; Medvedev, Ivan; Dolson, David; Nam, Hyun-Joo; O, Kenneth
2014-06-01
High resolution rotational spectroscopy enables chemical sensors that are both sensitive and highly specific, which is well suited for analysis of expired human breath. We have previously reported on detection of breath ethanol, methanol, acetone, and acetaldehyde using THz sensors. This paper will outline our present efforts in this area, with specific focus on our ongoing quest to correlate levels of blood glucose with concentrations of a few breath chemicals known to be affected by elevated blood sugar levels. Prospects, challenges and future plans will be outlined and discussed. Fosnight, A.M., B.L. Moran, and I.R. Medvedev, Chemical analysis of exhaled human breath using a terahertz spectroscopic approach. Applied Physics Letters, 2013. 103(13): p. 133703-5.
Tao, Lin; Ma, Jing; Kunisue, Tatsuya; Libelo, E Laurence; Tanabe, Shinsuke; Kannan, Kurunthachalam
2008-11-15
The occurrence of perfluorinated compounds (PFCs) in human blood is known to be widespread; nevertheless, the sources of exposure to humans, including infants, are not well understood. In this study, breast milk collected from seven countries in Asia was analyzed (n=184) for nine PFCs, including perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA). In addition, five brands of infant formula (n=21) and 11 brands of dairy milk (n=12) collected from retail stores in the United States were analyzed, for comparison with PFC concentrations previously reported for breast milk from the U.S. PFOS was the predominant PFC detected in almost all Asian breast milk samples, followed by perfluorohexanesulfonate (PFHxS) and PFOA. Median concentrations of PFOS in breast milk from Asian countries varied significantly;the lowest concentration of 39.4 pg/mL was found in India, and the highest concentration of 196 pg/mL was found in Japan. The measured concentrations were similarto or less than the concentrations previously reported from Sweden, the United States, and Germany (median, 106-166 pg/mL). PFHxS was found in more than 70% of the samples analyzed from Japan, Malaysia, Philippines, and Vietnam, at mean concentrations ranging from 6.45 (Malaysia) to 15.8 (Philippines) pg/mL PFOA was found frequently only in samples from Japan; the mean concentration for that country was 77.7 pg/mL. None of the PFCs were detected in the infant-formula or dairy-milk samples from the U.S. except a few samples that contained concentrations close to the limit of detection. The estimated average daily intake of PFOS by infants from seven Asian countries, via breastfeeding, was 11.8 +/- 10.6 ng/kg bw/ day; this value is 7-12 times higher than the estimated adult dietary intakes previously reported from Germany, Canada, and Spain. The average daily intake of PFOA by Japanese infants was 9.6 +/- 4.9 ng/kg bw/day, a value 3-10 times greater than the estimated adult dietary intakes reported from Germany and Canada. The highest estimated daily intakes of PFOS and PFOA by infants from seven Asian countries studied were 1-2 orders of magnitude below the tolerable daily intake values recommended by the U.K. Food Standards Agency.
Report of the Advisory Panel to the Mathematical and Information Science Directorate
1988-04-01
how to program S computers so that...Engineering, to expand the domain of behaviors we know how to program computers to perform to include more behaviors that previously only humans could do...technology? It is not easy to make clear the difference between making an advance in discovering how to program a behavior that no one knew how to program
ERIC Educational Resources Information Center
Knighton, Tamara; Hujaleh, Filsan; Iacampo, Joe; Werkneh, Gugsa
2009-01-01
This report is based on the Access and Support to Education and Training Survey (ASETS), which was undertaken by Statistics Canada in partnership with Human Resources and Skills Development Canada (HRSDC). The ASETS brings together three previous education surveys that covered specific population groups: (1) the Survey of Approaches to Educational…
First unusual case of keratitis in Europe due to the rare fungus Metarhizium anisopliae.
Dorin, Josephine; Debourgogne, Anne; Zaïdi, Mohamed; Bazard, Marie-Christine; Machouart, Marie
2015-05-01
Metarhizium anisopliae is a fungus utilized worldwide for insect-pest biocontrol. Few M. anisopliae infections have been reported previously. Here, M. anisopliae was isolated from a corneal ulcer in a healthy man. It is the first ocular case in France and Europe of this extremely rare fungus in humans. Copyright © 2015 Elsevier GmbH. All rights reserved.
2016-09-28
previous research and modeling results. The OMS and Perception Toolbox were used to perform a case study of an F18 mishap. Model results imply that...request documents from DTIC. Change of Address Organizations receiving reports from the U.S. Army Aeromedical Research Laboratory on automatic...54 Coriolis head movement during a coordinated turn. .............................................55 Case Study
Memory Accumulation Mechanisms in Human Cortex Are Independent of Motor Intentions
Tosoni, Annalisa; Mignogna, Valeria; McAvoy, Mark P.; Shulman, Gordon L.; Corbetta, Maurizio; Romani, Gian Luca
2014-01-01
Previous studies on perceptual decision-making have often emphasized a tight link between decisions and motor intentions. Human decisions, however, also depend on memories or experiences that are not closely tied to specific motor responses. Recent neuroimaging findings have suggested that, during episodic retrieval, parietal activity reflects the accumulation of evidence for memory decisions. It is currently unknown, however, whether these evidence accumulation signals are functionally linked to signals for motor intentions coded in frontoparietal regions and whether activity in the putative memory accumulator tracks the amount of evidence for only previous experience, as reflected in “old” reports, or for both old and new decisions, as reflected in the accuracy of memory judgments. Here, human participants used saccadic-eye and hand-pointing movements to report recognition judgments on pictures defined by different degrees of evidence for old or new decisions. A set of cortical regions, including the middle intraparietal sulcus, showed a monotonic variation of the fMRI BOLD signal that scaled with perceived memory strength (older > newer), compatible with an asymmetrical memory accumulator. Another set, including the hippocampus and the angular gyrus, showed a nonmonotonic response profile tracking memory accuracy (higher > lower evidence), compatible with a symmetrical accumulator. In contrast, eye and hand effector-specific regions in frontoparietal cortex tracked motor intentions but were not modulated by the amount of evidence for the effector outcome. We conclude that item recognition decisions are supported by a combination of symmetrical and asymmetrical accumulation signals largely segregated from motor intentions. PMID:24828652
A mouse model for a partially inactive obesity-associated human MC3R variant
Lee, Bonggi; Koo, Jashin; Yun Jun, Joo; Gavrilova, Oksana; Lee, Yongjun; Seo, Arnold Y.; Taylor-Douglas, Dezmond C.; Adler-Wailes, Diane C.; Chen, Faye; Gardner, Ryan; Koutzoumis, Dimitri; Sherafat Kazemzadeh, Roya; Roberson, Robin B.; Yanovski, Jack A.
2016-01-01
We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3RhWT/hWT) and double-mutant (C17A+G241A) human (MC3RhDM/hDM) MC3R, that MC3RhDM/hDM have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3RhWT/hWT. MC3RhDM/hDM mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3RhDM/hDM mice and MC3RhDM/hDM human subjects. MC3RhDM/hDM bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3RhWT/hWT MSCs. MC3RhDM/hDM impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development. PMID:26818770
Hand hygiene compliance rates: Fact or fiction?
McLaws, Mary-Louise; Kwok, Yen Lee Angela
2018-05-16
The mandatory national hand hygiene program requires Australian public hospitals to use direct human auditing to establish compliance rates. To establish the magnitude of the Hawthorne effect, we compared direct human audit rates with concurrent automated surveillance rates. A large tertiary Australian teaching hospital previously trialed automated surveillance while simultaneously performing mandatory human audits for 20 minutes daily on a medical and a surgical ward. Subtracting automated surveillance rates from human audit rates provided differences in percentage points (PPs) for each of the 3 quarterly reporting periods for 2014 and 2015. Direct human audit rates for the medical ward were inflated by an average of 55 PPs in 2014 and 64 PPs in 2015, 2.8-3.1 times higher than automated surveillance rates. The rates for the surgical ward were inflated by an average of 32 PPs in 2014 and 31 PPs in 2015, 1.6 times higher than automated surveillance rates. Over the 6 mandatory reporting quarters, human audits collected an average of 255 opportunities, whereas automation collected 578 times more data, averaging 147,308 opportunities per quarter. The magnitude of the Hawthorne effect on direct human auditing was not trivial and produced highly inflated compliance rates. Mandatory compliance necessitates accuracy that only automated surveillance can achieve, whereas daily hand hygiene ambassadors or reminder technology could harness clinicians' ability to hyperrespond to produce habitual compliance. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Chishti, Arif Ali; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther
Astronauts in space are exposed to a potentially harmful radiation field, which does not exist in its quality and quantity on earth. Radiation exposure in space can lead to delayed or acute health effects. A successful long-term space mission requires better risk estimation and development of appropriate countermeasures, therefore study of the cellular radiation response is necessary. Ionizing radiation can provoke active cellular responses (cell cycle arrest, DNA repair, apoptosis or other forms of cell type). Exposure to ionizing radiation also activates various signaling pathways in human cells. In the cellular radiation-response, two pivotal signal transduction pathways have to be comprehensively studied i.e. the p53-pathway and NF-κB-pathway. Discovery of fluorescent proteins has revolutionized biological research by making it possible to carry out functional studies in living cells and understanding complex signaling pathways. Previously the green fluorescent proteins EGFP and d2EGFP were used for signaling pathway studies. In this work the new red fluorescent protein tdTomato will be used for comprehensive investigation of NF-κB and other transcription factor activation after exposure of human cells to ionizing radiation (X-rays, heavy ions; space conditions). tdTomato has many advantages over EGFP because of its high fluorescence signals and a better signal/noise ratio in human cells. The previously constructed reporter system with d2EGFP was used to evaluate NF-kB activation after exposure to heavy ion particles of different biological effectiveness. The sensitivity threshold of this system was determined to be 2 particle traversals per cell nucleus. In the current study a more sensitive reporter assay will be constructed using a GAL4-VP16 turbo system that comprises a receptor plasmid and a reporter plasmid. This reporter assay will be designed and constructed with tdTomato and evaluation will be done with different molecular techniques.
Mashima, Izumi; Theodorea, Citra Fragrantia; Thaweboon, Boonyanit; Thaweboon, Sroisiri; Nakazawa, Futoshi
2016-01-01
Six Veillonella species have been frequently isolated from human oral cavities including infectious sites. Recently, it was reported that diet, smoking, and possibly socioeconomic status can influence the bacterial profile in oral cavities. In addition, oral hygiene habits may also influence oral microbiota in terms of both numbers and diversity of microorganisms. In this study, the identification of Veillonella species in tongue biofilms of Thai children, divided into three groups dependent on their status of oral hygiene. For this, we used a novel one-step PCR method with species-specific primer sets based on sequences of the rpoB gene. As shown in the results, the number of isolates of Veillonella species was 101 strains from only 10 of 89 subjects. However, the total number of bacteria was high for all subjects. Since it was reported in previous studies that Veillonella species were easy to isolate in human tongue biofilms at high numbers, the results obtained in this study may suggest country- or age-specific differences. Moreover, Veillonella species were detected predominantly in subjects who had poor oral hygiene compared to those with good or moderate oral hygiene. From these results, there is a possibility that Veillonella species may be an index of oral hygiene status. Furthermore, V. rogosae was a predominant species in tongue biofilms of Thai children, whereas V. parvula and V. denticariosi were not isolated at all. These characteristics of the distribution and frequency of Veillonella species are similar to those reported in previous studies. Although further studies are needed in other countries, in this study, a successful novel one-step PCR method was established to detect Veillonella species in human oral cavities easily and effectively. Furthermore, this is the first report investigating the distribution and frequency of Veillonella species in tongue biofilms of Thai children. PMID:27326455
Mellough, Carla B; Sernagor, Evelyne; Moreno-Gimeno, Inmaculada; Steel, David H W; Lako, Majlinda
2012-04-01
Recent successes in the stem cell field have identified some of the key chemical and biological cues which drive photoreceptor derivation from human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC); however, the efficiency of this process is variable. We have designed a three-step photoreceptor differentiation protocol combining previously published methods that direct the differentiation of hESC and hiPSC toward a retinal lineage, which we further modified with additional supplements selected on the basis of reports from the eye field and retinal development. We report that hESC and hiPSC differentiating under our regimen over a 60 day period sequentially acquire markers associated with neural, retinal field, retinal pigmented epithelium and photoreceptor cells, including mature photoreceptor markers OPN1SW and RHODOPSIN with a higher efficiency than previously reported. In addition, we report the ability of hESC and hiPSC cultures to generate neural and retinal phenotypes under minimal culture conditions, which may be linked to their ability to endogenously upregulate the expression of a range of factors important for retinal cell type specification. However, cultures that were differentiated with full supplementation under our photoreceptor-induction regimen achieve this within a significantly shorter time frame and show a substantial increase in the expression of photoreceptor-specific markers in comparison to cultures differentiated under minimal conditions. Interestingly, cultures supplemented only with B27 and/or N2 displayed comparable differentiation efficiency to those under full supplementation, indicating a key role for B27 and N2 during the differentiation process. Furthermore, our data highlight an important role for Dkk1 and Noggin in enhancing the differentiation of hESC and hiPSC toward retinal progenitor cells and photoreceptor precursors during the early stages of differentiation, while suggesting that further maturation of these cells into photoreceptors may not require additional factors and can ensue under minimal culture conditions. Copyright © 2012 AlphaMed Press.
Ancient gene flow from early modern humans into Eastern Neanderthals
Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J.; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A.; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M.; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi
2016-01-01
It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here, we analyze the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and of modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously reported. PMID:26886800
Multispectral index for the remote detection of human skin signatures
NASA Astrophysics Data System (ADS)
Baranoski, Gladimir V. G.; Chen, Tenn F.
2015-07-01
We propose a multispectral index to assist the detection of human signatures in complex natural environments. Differently from previously proposed indices, it takes into account the spectral responses of human skin not only in the near infrared, but also in the visible region of the light spectrum. As a result, it can contribute to mitigate the chances of false alarms during time-critical search and rescue operations carried out in such environments. Our investigation is supported by the use of reflectance data measured for different skin specimens and natural materials such as sand, ocean water, melting snow, and forest vegetation. We believe that the observations reported in this work can be incorporated into the design of more effective procedures and devices for the differentiation of human targets from background materials commonly found in nature.
Lafferty, Kevin D.; Hopkins, Skylar R.
2018-01-01
Having split early from Gondwana, Zealandia (now modern New Zealand) escaped discovery until the late 13th century, and therefore remains an important glimpse into a human-free world. Without humans or other land mammals, diverse and peculiar birds evolved in isolation, including several flightless moa species, the giant pouakai eagle (Harpagornis moorei), the kiwi (Apteryx mantelli), and the kakapo parrot (Strigops habroptila). This unique community has fascinated paleoecologists, who have spent almost two centuries devising new ways to glean information from ancient bird remains. In PNAS, Boast et al. (1) apply one recent technological advance, ancient DNA (aDNA) metabarcoding, to confirm previous discoveries and report new details about moa and kakapo diets, parasites, and niches. Their efforts confirm Zealandia was a lot different before humans arrived.
Williamson, Sarah L; Giudici, Laura; Kilstrup-Nielsen, Charlotte; Gold, Wendy; Pelka, Gregory J; Tam, Patrick P L; Grimm, Andrew; Prodi, Dionigio; Landsberger, Nicoletta; Christodoulou, John
2012-02-01
The X-linked cyclin-dependent kinase-like 5 (CDKL5) gene is an important molecular determinant of early-onset intractable seizures with infantile spasms and Rett syndrome-like phenotype. The gene encodes a kinase that may influence components of molecular pathways associated with MeCP2. In humans there are two previously reported splice variants that differ in the 5' untranslated exons and produce the same 115 kDa protein. Furthermore, very recently, a novel transcript including a novel exon (16b) has been described. By aligning both the human and mouse CDKL5 proteins to the orthologs of other species, we identified a theoretical 107 kDa isoform with an alternative C-terminus that terminates in intron 18. In human brain and all other tissues investigated except the testis, this novel isoform is the major CDKL5 transcript. The detailed characterisation of this novel isoform of CDKL5 reveals functional and subcellular localisation attributes that overlap greatly, but not completely, with that of the previously studied human CDKL5 protein. Considering its predominant expression in the human and mouse brain, we believe that this novel isoform is likely to be of primary pathogenic importance in human diseases associated with CDKL5 deficiency, and suggest that screening of the related intronic sequence should be included in the molecular genetic analyses of patients with a suggestive clinical phenotype.
Russell, J. L.; Lyn, H.; Schaeffer, J. A.; Hopkins, W. D.
2011-01-01
The cultural intelligence hypothesis (CIH) claims that humans' advanced cognition is a direct result of human culture and that children are uniquely specialized to absorb and utilize this cultural experience (Tomasello, 2000). Comparative data demonstrating that 2.5 year old human children outperform apes on measures of social cognition but not on measures of physical cognition support this claim (E. Herrmann, J. Call, M. V. Hernandez-Lloreda, B. Hare, & M. Tomasello, 2007). However, the previous study failed to control for rearing when comparing these two species. Specifically, the human children were raised in a human culture whereas the apes were raised in standard sanctuary settings. To further explore the CIH, here we compared the performance on multiple measures of social and physical cognition in a group of standard reared apes raised in conditions typical of zoo and biomedical laboratory settings to that of apes reared in an enculturated socio-communicatively rich environment. Overall, the enculturated apes significantly outperformed their standard reared counterparts on the cognitive tasks and this was particularly true for measures of communication. Furthermore, the performance of the enculturated apes was very similar to previously reported data from 2.5 year old children. We conclude that apes who are reared in a human-like socio-communicatively rich environment develop superior communicative abilities compared to apes reared in standard laboratory settings, which supports some assumptions of the cultural intelligence hypothesis. PMID:22010903
Chou, Bin-Kuan; Gu, Haihui; Gao, Yongxing; Dowey, Sarah N.; Wang, Ying; Shi, Jun; Li, Yanxin; Ye, Zhaohui; Cheng, Tao
2015-01-01
Reprogramming human adult blood mononuclear cells (MNCs) cells by transient plasmid expression is becoming increasingly popular as an attractive method for generating induced pluripotent stem (iPS) cells without the genomic alteration caused by genome-inserting vectors. However, its efficiency is relatively low with adult MNCs compared with cord blood MNCs and other fetal cells and is highly variable among different adult individuals. We report highly efficient iPS cell derivation under clinically compliant conditions via three major improvements. First, we revised a combination of three EBNA1/OriP episomal vectors expressing five transgenes, which increased reprogramming efficiency by ≥10–50-fold from our previous vectors. Second, human recombinant vitronectin proteins were used as cell culture substrates, alleviating the need for feeder cells or animal-sourced proteins. Finally, we eliminated the previously critical step of manually picking individual iPS cell clones by pooling newly emerged iPS cell colonies. Pooled cultures were then purified based on the presence of the TRA-1-60 pluripotency surface antigen, resulting in the ability to rapidly expand iPS cells for subsequent applications. These new improvements permit a consistent and reliable method to generate human iPS cells with minimal clonal variations from blood MNCs, including previously difficult samples such as those from patients with paroxysmal nocturnal hemoglobinuria. In addition, this method of efficiently generating iPS cells under feeder-free and xeno-free conditions allows for the establishment of clinically compliant iPS cell lines for future therapeutic applications. PMID:25742692
Bonmatí, Alejandro; Gómez-Olivencia, Asier; Arsuaga, Juan-Luis; Carretero, José Miguel; Gracia, Ana; Martínez, Ignacio; Lorenzo, Carlos; Bérmudez de Castro, José María; Carbonell, Eudald
2010-10-26
We report a nearly complete lumbar spine from the Middle Pleistocene site of the Sima de los Huesos (SH) that is assigned to the previously published SH male Pelvis 1 [Arsuaga JL, et al. (1999). Nature 399: 255-258]. The "SH Pelvis 1 individual" is a unique nearly complete lumbo-pelvic complex from the human Middle Pleistocene fossil record, and offers a rare glimpse into the anatomy and past lifeways of Homo heidelbergensis. A revised reconstruction of Pelvis 1, together with the current fossil evidence, confirms our previous hypothesis that the morphology of this pelvis represents the primitive pattern within the genus Homo. Here we argue that this primitive pattern is also characterized by sexual dimorphism in the pelvic canal shape, implying complicated deliveries. In addition, this individual shows signs of lumbar kyphotic deformity, spondylolisthesis, and Baastrup disease. This suite of lesions would have postural consequences and was most likely painful. As a result, the individual's daily physical activities would have been restricted to some extent. Reexamination of the age-at-death agrees with this individual being over 45 y old, relying on the modern human pattern of changes of the articular surfaces of the os coxae. The presence of degenerative pathological lesions and the advanced age-at-death of this individual make it the most ancient postcranial evidence of an aged individual in the human fossil record. Additional nonpathological SH lumbo-pelvic remains are consistent with previous hypotheses, suggesting a less-pronounced sagittal spinal curvature in Neandertals compared with Homo sapiens.
Bonmatí, Alejandro; Gómez-Olivencia, Asier; Arsuaga, Juan-Luis; Carretero, José Miguel; Gracia, Ana; Martínez, Ignacio; Lorenzo, Carlos; Bérmudez de Castro, José María; Carbonell, Eudald
2010-01-01
We report a nearly complete lumbar spine from the Middle Pleistocene site of the Sima de los Huesos (SH) that is assigned to the previously published SH male Pelvis 1 [Arsuaga JL, et al. (1999). Nature 399: 255–258]. The “SH Pelvis 1 individual” is a unique nearly complete lumbo-pelvic complex from the human Middle Pleistocene fossil record, and offers a rare glimpse into the anatomy and past lifeways of Homo heidelbergensis. A revised reconstruction of Pelvis 1, together with the current fossil evidence, confirms our previous hypothesis that the morphology of this pelvis represents the primitive pattern within the genus Homo. Here we argue that this primitive pattern is also characterized by sexual dimorphism in the pelvic canal shape, implying complicated deliveries. In addition, this individual shows signs of lumbar kyphotic deformity, spondylolisthesis, and Baastrup disease. This suite of lesions would have postural consequences and was most likely painful. As a result, the individual’s daily physical activities would have been restricted to some extent. Reexamination of the age-at-death agrees with this individual being over 45 y old, relying on the modern human pattern of changes of the articular surfaces of the os coxae. The presence of degenerative pathological lesions and the advanced age-at-death of this individual make it the most ancient postcranial evidence of an aged individual in the human fossil record. Additional nonpathological SH lumbo-pelvic remains are consistent with previous hypotheses, suggesting a less-pronounced sagittal spinal curvature in Neandertals compared with Homo sapiens. PMID:20937858
Estimations of the lethal and exposure doses for representative methanol symptoms in humans.
Moon, Chan-Seok
2017-01-01
The aim of this review was to estimate the lethal and exposure doses of a representative symptom (blindness) of methanol exposure in humans by reviewing data from previous articles. Available articles published from 1970 to 2016 that investigated the dose-response relationship for methanol exposure (i.e., the exposure concentration and the biological markers/clinical symptoms) were evaluated; the MEDLINE and RISS (Korean search engine) databases were searched. The available data from these articles were carefully selected to estimate the range and median of a lethal human dose. The regression equation and correlation coefficient (between the exposure level and urinary methanol concentration as a biological exposure marker) were assumed from the previous data. The lethal human dose of pure methanol was estimated at 15.8-474 g/person as a range and as 56.2 g/person as the median. The dose-response relationship between methanol vapor in ambient air and urinary methanol concentrations was thought to be correlated. An oral intake of 3.16-11.85 g/person of pure methanol could cause blindness. The lethal dose from respiratory intake was reported to be 4000-13,000 mg/l. The initial concentration of optic neuritis and blindness were shown to be 228.5 and 1103 mg/l, respectively, for a 12-h exposure. The concentration of biological exposure indices and clinical symptoms for methanol exposure might have a dose-response relationship according to previous articles. Even a low dose of pure methanol through oral or respiratory exposure might be lethal or result in blindness as a clinical symptom.
Faughn, Carley; Marrus, Natasha; Shuman, Jeremy; Ross, Stephen R; Constantino, John N; Pruett, John R; Povinelli, Daniel J
2015-05-01
Comparative studies of social responsiveness, a core impairment in autism spectrum disorder (ASD), will enhance our understanding of typical and atypical social behavior. We previously reported a quantitative, cross-species (human-chimpanzee) social responsiveness measure, which included the development of the Chimpanzee Social Responsiveness Scale (CSRS). Here, we augment our prior CSRS sample with 25 zoo chimpanzees at three sites: combined N = 54. The CSRS demonstrated strong interrater reliability, and low-ranked chimpanzees, on average, displayed higher CSRS scores. The CSRS continues to discriminate variation in chimpanzee social responsiveness, and the association of higher scores with lower chimpanzee social standing has implications for the relationship between autistic traits and human social status. Continued comparative investigations of social responsiveness will enhance our understanding of underlying impairments in ASD, improve early diagnosis, and inform future therapies.
Xiao, Lifu; Tian, Xiumei; Harihar, Sitaram; Li, Qifei; Li, Li; Welch, Danny R; Zhou, Anhong
2017-06-15
There has been an interest in developing multimodal approaches to combine the advantages of individual imaging modalities, as well as to compensate for respective weaknesses. We previously reported a composite nano-system composed of gadolinium-doped mesoporous silica nanoparticle and gold nanoparticle (Gd-Au NPs) as an efficient MRI contrast agent for in vivo cancer imaging. However, MRI lacks sensitivity and is unsuitable for in vitro cancer detection. Thus, here we performed a study to use the Gd-Au NPs for detection and imaging of a widely recognized human cancer biomarker, epidermal growth factor receptor (EGFR), in individual human cancer cells with surface-enhanced Raman scattering (SERS). The Gd-Au NPs were sequentially conjugated with a monoclonal antibody recognizing EGFR and a Raman reporter molecule, 4-meraptobenzoic acid (MBA), to generate a characteristic SERS signal at 1075cm -1 . By spatially mapping the SERS intensity at 1075cm -1 , cellular distribution of EGFR and its relocalization on the plasma membrane were measured in situ. In addition, the EGFR expression levels in three human cancer cell lines (S18, A431 and A549) were measured using this SERS probe, which were consistent with the comparable measurements using immunoblotting and immunofluorescence. Our SERS results show that functionalized Gd-Au NPs successfully targeted EGFR molecules in three human cancer cell lines and monitored changes in single cell EGFR distribution in situ, demonstrating its potential to study cell activity under physiological conditions. This SERS study, combined with our previous MRI study, suggests the Gd-Au nanocomposite is a promising candidate contrast agent for multimodal cancer imaging. Copyright © 2017 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Xiao, Lifu; Tian, Xiumei; Harihar, Sitaram; Li, Qifei; Li, Li; Welch, Danny R.; Zhou, Anhong
2017-06-01
There has been an interest in developing multimodal approaches to combine the advantages of individual imaging modalities, as well as to compensate for respective weaknesses. We previously reported a composite nano-system composed of gadolinium-doped mesoporous silica nanoparticle and gold nanoparticle (Gd-Au NPs) as an efficient MRI contrast agent for in vivo cancer imaging. However, MRI lacks sensitivity and is unsuitable for in vitro cancer detection. Thus, here we performed a study to use the Gd-Au NPs for detection and imaging of a widely recognized human cancer biomarker, epidermal growth factor receptor (EGFR), in individual human cancer cells with surface-enhanced Raman scattering (SERS). The Gd-Au NPs were sequentially conjugated with a monoclonal antibody recognizing EGFR and a Raman reporter molecule, 4-meraptobenzoic acid (MBA), to generate a characteristic SERS signal at 1075 cm- 1. By spatially mapping the SERS intensity at 1075 cm- 1, cellular distribution of EGFR and its relocalization on the plasma membrane were measured in situ. In addition, the EGFR expression levels in three human cancer cell lines (S18, A431 and A549) were measured using this SERS probe, which were consistent with the comparable measurements using immunoblotting and immunofluorescence. Our SERS results show that functionalized Gd-Au NPs successfully targeted EGFR molecules in three human cancer cell lines and monitored changes in single cell EGFR distribution in situ, demonstrating its potential to study cell activity under physiological conditions. This SERS study, combined with our previous MRI study, suggests the Gd-Au nanocomposite is a promising candidate contrast agent for multimodal cancer imaging.
Van Vinh Chau, Nguyen; Buu Chau, Le; Desquesnes, Marc; Herder, Stephane; Phu Huong Lan, Nguyen; Campbell, James I.; Van Cuong, Nguyen; Yimming, Benjarat; Chalermwong, Piangjai; Jittapalapong, Sathaporn; Ramon Franco, Jose; Tri Tue, Ngo; Rabaa, Maia A.; Carrique-Mas, Juan; Pham Thi Thanh, Tam; Tran Vu Thieu, Nga; Berto, Alessandra; Thi Hoa, Ngo; Van Minh Hoang, Nguyen; Canh Tu, Nguyen; Khac Chuyen, Nguyen; Wills, Bridget; Tinh Hien, Tran; Thwaites, Guy E.; Yacoub, Sophie; Baker, Stephen
2016-01-01
Background. Trypanosoma is a genus of unicellular parasitic flagellate protozoa. Trypanosoma brucei species and Trypanosoma cruzi are the major agents of human trypanosomiasis; other Trypanosoma species can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma. Methods. Microscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source. Results. PCR amplification and serological testing identified the infecting species as Trypanosoma evansi. Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive for T. evansi. Conclusions. We report the first laboratory-confirmed case of T. evansi in a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden of T. evansi in local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases. PMID:26908809
Jennings, Rosalind M; Malbon, C; Brock, F; Harrisson, S E; Carr, D J
2018-05-21
The aim of this paper was to examine any injuries from posterior behind armour blunt trauma ballistic impacts directly over the spine onto typical hard body armours. Due to the spine being close to the surface of the skin and a lack of any previous specific research into this topic, this study was designed to gain preliminary insight into the mechanisms involved and injuries caused. Pigs were chosen as the closest representative of human spine, tissue and skin, although their spines are deeper under the surface than humans. Baseline spine and ribs shots were conducted to ensure that the study was effective. This study used a 65 kg cadaveric pig eviscerated torso and 7.62 NATO ammunition (7.62×51; L2A2; mean velocity=838 m/s, SD=4 m/s) impacting hard body armour plates over the spine. Injuries were inspected, and sections were removed for X-ray and micro-CT assessment. There was no visible soft tissue damage under the impact point on the armour over the spine, and no bony injuries were reported. Baseline rib shots resulted in multiple rib fractures; some showed minimal displacement of the bone. Baseline spine shot resulted in damage across the spine involving spinal cord and bone. No injuries were noted from the spinal impacts, and the rib shots resulted in injuries consistent with those previously reported. The anatomical differences between pigs and humans does not preclude that bony injuries could occur in a human from these types of spinal ballistic impacts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Removal of Thelazia callipaeda from the subconjunctival space.
Yagi, T; Sasoh, M; Kawano, T; Ito, K; Uji, Y; Ando, K
2007-01-01
To report the finding of Thelazia callipaeda within the human subconjunctival space. An 81-year-old man with a history of traumatic conjunctival laceration that occurred 2 years previously had white worms in the subconjunctival space of his right eye. Five worms were removed from the subconjunctival space via a local peritomy, since there was no conjunctival laceration noted during the examination. These worms were identified as T callipaeda. T callipaeda cannot dig holes in the ocular wall due to the lack of hooks or sharp spines within the mouth. Therefore, the authors speculate that these worms entered the subconjunctival space through a conjunctival laceration that had occurred 2 years previously.
RESIDUAL RISK ASSESSMENTS - RESIDUAL RISK ...
This source category previously subjected to a technology-based standard will be examined to determine if health or ecological risks are significant enough to warrant further regulation for Coke Ovens. These assesments utilize existing models and data bases to examine the multi-media and multi-pollutant impacts of air toxics emissions on human health and the environment. Details on the assessment process and methodologies can be found in EPA's Residual Risk Report to Congress issued in March of 1999 (see web site). To assess the health risks imposed by air toxics emissions from Coke Ovens to determine if control technology standards previously established are adequately protecting public health.
Joscelyne, Amy; Knuckey, Sarah; Satterthwaite, Margaret L; Bryant, Richard A; Li, Meng; Qian, Meng; Brown, Adam D
2015-01-01
Human rights advocates play a critical role in promoting respect for human rights world-wide, and engage in a broad range of strategies, including documentation of rights violations, monitoring, press work and report-writing, advocacy, and litigation. However, little is known about the impact of human rights work on the mental health of human rights advocates. This study examined the mental health profile of human rights advocates and risk factors associated with their psychological functioning. 346 individuals currently or previously working in the field of human rights completed an internet-based survey regarding trauma exposure, depression, posttraumatic stress disorder (PTSD), resilience and occupational burnout. PTSD was measured with the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) and depression was measured with the Patient History Questionnaire-9 (PHQ-9). These findings revealed that among human rights advocates that completed the survey, 19.4% met criteria for PTSD, 18.8% met criteria for subthreshold PTSD, and 14.7% met criteria for depression. Multiple linear regressions revealed that after controlling for symptoms of depression, PTSD symptom severity was predicted by human rights-related trauma exposure, perfectionism and negative self-appraisals about human rights work. In addition, after controlling for symptoms of PTSD, depressive symptoms were predicted by perfectionism and lower levels of self-efficacy. Survey responses also suggested high levels of resilience: 43% of responders reported minimal symptoms of PTSD. Although survey responses suggest that many human rights workers are resilient, they also suggest that human rights work is associated with elevated rates of PTSD and depression. The field of human rights would benefit from further empirical research, as well as additional education and training programs in the workplace about enhancing resilience in the context of human rights work.
Joscelyne, Amy; Knuckey, Sarah; Satterthwaite, Margaret L.; Bryant, Richard A.; Li, Meng; Qian, Meng; Brown, Adam D.
2015-01-01
Human rights advocates play a critical role in promoting respect for human rights world-wide, and engage in a broad range of strategies, including documentation of rights violations, monitoring, press work and report-writing, advocacy, and litigation. However, little is known about the impact of human rights work on the mental health of human rights advocates. This study examined the mental health profile of human rights advocates and risk factors associated with their psychological functioning. 346 individuals currently or previously working in the field of human rights completed an internet-based survey regarding trauma exposure, depression, posttraumatic stress disorder (PTSD), resilience and occupational burnout. PTSD was measured with the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) and depression was measured with the Patient History Questionnaire-9 (PHQ-9). These findings revealed that among human rights advocates that completed the survey, 19.4% met criteria for PTSD, 18.8% met criteria for subthreshold PTSD, and 14.7% met criteria for depression. Multiple linear regressions revealed that after controlling for symptoms of depression, PTSD symptom severity was predicted by human rights-related trauma exposure, perfectionism and negative self-appraisals about human rights work. In addition, after controlling for symptoms of PTSD, depressive symptoms were predicted by perfectionism and lower levels of self-efficacy. Survey responses also suggested high levels of resilience: 43% of responders reported minimal symptoms of PTSD. Although survey responses suggest that many human rights workers are resilient, they also suggest that human rights work is associated with elevated rates of PTSD and depression. The field of human rights would benefit from further empirical research, as well as additional education and training programs in the workplace about enhancing resilience in the context of human rights work. PMID:26700305
A case of severe anal injury in an adolescent male due to bestial sexual experimentation.
Blevins, Roger O
2009-10-01
This report delineates a case of anal injury in a 12-year-old boy who gave a detailed history of bestial behavior with a male bulldog. The child described how he had seen this behavior modeled on the internet and subsequently initiated contact with his own dog, causing the dog to penetrate him anally. This type of juvenile bestial behavior with injury has only been reported once previously in the medical literature. Zoophilia, along with a number of other paraphilias, frequently has its onset in the adolescent age group. Adolescents evidencing paraphilic behaviors require thorough psychological evaluation. Spontaneous sexual assault of a human by a canine has never been described in the human or veterinary medical literature, nor is such a thing likely. A clinician involved in evaluating serious ano-genital injury in a child reportedly due to spontaneous canine sexual assault must consider other possible traumatic etiologies including sexual abuse. Investigation in any such case is essential. 2009 Elsevier Ltd and Faculty of Forensic and Legal Medicine.
Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML
Zaitseva, Lyubov; Murray, Megan Y.; Shafat, Manar S.; Lawes, Matthew J.; MacEwan, David J.; Bowles, Kristian M.; Rushworth, Stuart A.
2014-01-01
Pharmacological targeting of BTK using ibrutinib has recently shown encouraging clinical activity in a range of lymphoid malignancies. Recently we reported that ibrutinib inhibits human acute myeloid leukemia (AML) blast proliferation and leukemic cell adhesion to the surrounding bone marrow stroma cells. Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo. It has previously been shown that SDF1/CXCR4-induced migration is dependent on activation of downstream BTK in chronic lymphocytic leukaemia (CLL) and multiple myeloma. Here we show that SDF-1 induces BTK phosphorylation and downstream MAPK signalling in primary AML blast. Furthermore, we show that ibrutinib can inhibit SDF1-induced AKT and MAPK activation. These results reported here provide a molecular mechanistic rationale for clinically evaluating BTK inhibition in AML patients and suggests that in some AML patients the blasts count may initially rise in response to ibrutinib therapy, analgous to similar clinical observations in CLL. PMID:25294819
Novel mutation of Endothelin-B receptor gene in Waardenburg-Hirschsprung disease.
Sangkhathat, Surasak; Chiengkriwate, Piyawan; Kusafuka, Takeshi; Patrapinyokul, Sakda; Fukuzawa, Masahiro
2005-12-01
Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance. We investigated a case of WS4 together with all members of her nuclear family for the alteration of the EDNRB gene by using PCR-SSCP and direct sequencing technique. The index patient, who was born to a family with no history of Hirschsprung disease, presented total colonic aganglionosis with small bowel extension, sensorineural hearing loss and generalized cutaneous pigmentary defects. Interestingly, both irides were normally black. The study detected a homozygous missense mutation at codon 196 in exon 2 (Ser196Asn), which has not been reported. Both parents and four in six siblings harbored heterozygous mutation without any clinical manifestation. Our findings were consistent with previous observations that full spectrum of WS4 occurred to the mutate homozygotes. Moreover, the non-penetrance of heterozygotes in our pedigree, which differs from other reports, demonstrates the high pleiotropic effect of EDNRB mutations in human.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dougan, A; Dreicer, M; Essner, J
2009-11-16
In 2009, Lawrence Livermore National Laboratory (LLNL) engaged in several activities to support NA-24's Next Generation Safeguards Initiative (NGSI). This report outlines LLNL's efforts to support Human Capital Development (HCD), one of five key components of NGSI managed by Dunbar Lockwood in the Office of International Regimes and Agreements (NA-243). There were five main LLNL summer safeguards HCD efforts sponsored by NGSI: (1) A joint Monterey Institute of International Studies/Center for Nonproliferation Studies-LLNL International Safeguards Policy and Information Analysis Course; (2) A Summer Safeguards Policy Internship Program at LLNL; (3) A Training in Environmental Sample Analysis for IAEA Safeguards Internship;more » (4) Safeguards Technology Internships; and (5) A joint LLNL-INL Summer Safeguards Lecture Series. In this report, we provide an overview of these five initiatives, an analysis of lessons learned, an update on the NGSI FY09 post-doc, and an update on students who participated in previous NGSI-sponsored LLNL safeguards HCD efforts.« less
Mapping the zoonotic niche of Ebola virus disease in Africa
Pigott, David M; Golding, Nick; Mylne, Adrian; Huang, Zhi; Henry, Andrew J; Weiss, Daniel J; Brady, Oliver J; Kraemer, Moritz UG; Smith, David L; Moyes, Catherine L; Bhatt, Samir; Gething, Peter W; Horby, Peter W; Bogoch, Isaac I; Brownstein, John S; Mekaru, Sumiko R; Tatem, Andrew J; Khan, Kamran; Hay, Simon I
2014-01-01
Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976–2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past. DOI: http://dx.doi.org/10.7554/eLife.04395.001 PMID:25201877
Park, Subok; Gallas, Bradon D; Badano, Aldo; Petrick, Nicholas A; Myers, Kyle J
2007-04-01
A previous study [J. Opt. Soc. Am. A22, 3 (2005)] has shown that human efficiency for detecting a Gaussian signal at a known location in non-Gaussian distributed lumpy backgrounds is approximately 4%. This human efficiency is much less than the reported 40% efficiency that has been documented for Gaussian-distributed lumpy backgrounds [J. Opt. Soc. Am. A16, 694 (1999) and J. Opt. Soc. Am. A18, 473 (2001)]. We conducted a psychophysical study with a number of changes, specifically in display-device calibration and data scaling, from the design of the aforementioned study. Human efficiency relative to the ideal observer was found again to be approximately 5%. Our variance analysis indicates that neither scaling nor display made a statistically significant difference in human performance for the task. We conclude that the non-Gaussian distributed lumpy background is a major factor in our low human-efficiency results.
Imaging shear stress distribution and evaluating the stress concentration factor of the human eye
NASA Astrophysics Data System (ADS)
Joseph Antony, S.
2015-03-01
Healthy eyes are vital for a better quality of human life. Historically, for man-made materials, scientists and engineers use stress concentration factors to characterise the effects of structural non-homogeneities on their mechanical strength. However, such information is scarce for the human eye. Here we present the shear stress distribution profiles of a healthy human cornea surface in vivo using photo-stress analysis tomography, which is a non-intrusive and non-X-ray based method. The corneal birefringent retardation measured here is comparable to that of previous studies. Using this, we derive eye stress concentration factors and the directional alignment of major principal stress on the surface of the cornea. Similar to thermometers being used for monitoring the general health in humans, this report provides a foundation to characterise the shear stress carrying capacity of the cornea, and a potential bench mark for validating theoretical modelling of stresses in the human eye in future.
Sulphation of acetaminophen by the human cytosolic sulfotransferases: a systematic analysis
Yamamoto, Akihiro; Liu, Ming-Yih; Kurogi, Katsuhisa; Sakakibara, Yoichi; Saeki, Yuichi; Suiko, Masahito; Liu, Ming-Cheh
2015-01-01
Sulphation is known to be critically involved in the metabolism of acetaminophen in vivo. This study aimed to systematically identify the major human cytosolic sulfotransferase (SULT) enzyme(s) responsible for the sulphation of acetaminophen. A systematic analysis showed that three of the twelve human SULTs, SULT1A1, SULT1A3 and SULT1C4, displayed the strongest sulphating activity towards acetaminophen. The pH dependence of the sulphation of acetaminophen by each of these three SULTs was examined. Kinetic parameters of these three SULTs in catalysing acetaminophen sulphation were determined. Moreover, sulphation of acetaminophen was shown to occur in HepG2 human hepatoma cells and Caco-2 human intestinal epithelial cells under the metabolic setting. Of the four human organ samples tested, liver and intestine cytosols displayed considerably higher acetaminophen-sulphating activity than those of lung and kidney. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of acetaminophen in vivo previously reported. PMID:26067475
Navigating a social world with robot partners: A quantitative cartography of the Uncanny Valley.
Mathur, Maya B; Reichling, David B
2016-01-01
Android robots are entering human social life. However, human-robot interactions may be complicated by a hypothetical Uncanny Valley (UV) in which imperfect human-likeness provokes dislike. Previous investigations using unnaturally blended images reported inconsistent UV effects. We demonstrate an UV in subjects' explicit ratings of likability for a large, objectively chosen sample of 80 real-world robot faces and a complementary controlled set of edited faces. An "investment game" showed that the UV penetrated even more deeply to influence subjects' implicit decisions concerning robots' social trustworthiness, and that these fundamental social decisions depend on subtle cues of facial expression that are also used to judge humans. Preliminary evidence suggests category confusion may occur in the UV but does not mediate the likability effect. These findings suggest that while classic elements of human social psychology govern human-robot social interaction, robust UV effects pose a formidable android-specific problem. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Simple Monitoring of Gene Targeting Efficiency in Human Somatic Cell Lines Using the PIGA Gene
Karnan, Sivasundaram; Konishi, Yuko; Ota, Akinobu; Takahashi, Miyuki; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki
2012-01-01
Gene targeting in most of human somatic cell lines has been labor-intensive because of low homologous recombination efficiency. The development of an experimental system that permits a facile evaluation of gene targeting efficiency in human somatic cell lines is the first step towards the improvement of this technology and its application to a broad range of cell lines. In this study, we utilized phosphatidylinositol glycan anchor biosynthesis class A (PIGA), a gene essential for the synthesis of glycosylphosphatidyl inositol (GPI) anchors, as a reporter of gene targeting events in human somatic cell lines. Targeted disruption of PIGA was quantitatively detected with FLAER, a reagent that specifically binds to GPI anchors. Using this PIGA-based reporter system, we successfully detected adeno-associated virus (AAV)-mediated gene targeting events both with and without promoter-trap enrichment of gene-targeted cell population. The PIGA-based reporter system was also capable of reproducing previous findings that an AAV-mediated gene targeting achieves a remarkably higher ratio of homologous versus random integration (H/R ratio) of targeting vectors than a plasmid-mediated gene targeting. The PIGA-based system also detected an approximately 2-fold increase in the H/R ratio achieved by a small negative selection cassette introduced at the end of the AAV-based targeting vector with a promoter-trap system. Thus, our PIGA-based system is useful for monitoring AAV-mediated gene targeting and will assist in improving gene targeting technology in human somatic cell lines. PMID:23056640
Qin, Meng; Guan, Xin; Zhang, Yu; Shen, Bin; Liu, Fang; Zhang, Qingyu; Ma, Yupo; Jiang, Yongping
2018-01-22
Autologous transplantation of endothelial progenitor cells (EPCs) is a promising therapeutic approach in the treatment of various vascular diseases. We previously reported a two-step culture system for scalable generation of human EPCs derived from cord blood CD34 + cells ex vivo. Here, we now apply this culture system to expand and differentiate human and nonhuman primate EPCs from mobilized peripheral blood (PB) CD34 + cells for the therapeutic potential of autologous transplantation. The human and nonhuman primate EPCs from mobilized PB CD34 + cells were cultured according to our previously reported system. The generated adherent cells were then characterized by the morphology, surface markers, nitric oxide (NO)/endothelial NO synthase (eNOS) levels and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake/fluorescein isothiocyanate (FITC)-lectin binding actives. Furthermore, the efficacy and safety studies were performed by autologous transplantation via hepatic portal vein injection in a nonhuman primate model with acute liver sinusoidal endothelial cell injury. The mobilized PB CD34 + cells from both human and nonhuman primate were efficiently expanded and differentiated. Over 2 × 10 8 adherent cells were generated from 20 mL mobilized primate PB (1.51 × 10 6 ± 3.39 × 10 5 CD34 + cells) by 36-day culture and more than 80% of the produced cells were identified as EPCs/endothelial cells (ECs). In the autologous transplant model, the injected EPC/ECs from nonhuman primate PB were scattered in the intercellular spaces of hepatocytes at the hepatic tissues 14 days post-transplantation, indicating successful migration and reconstitution in the liver structure as the functional EPCs/ECs. We successfully applied our previous two-step culture system for the generation of primate EPCs from mobilized PB CD34 + cells, evaluated the phenotypes ex vivo, and transplanted autologous EPCs/ECs in a nonhuman primate model. Our study indicates that it may be possible for these ex-vivo high-efficient expanded EPCs to be used in clinical cell therapy.
Evidence for hubs in human functional brain networks
Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E
2013-01-01
Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601
Sluch, Valentin M; Chamling, Xitiz; Liu, Melissa M; Berlinicke, Cynthia A; Cheng, Jie; Mitchell, Katherine L; Welsbie, Derek S; Zack, Donald J
2017-11-01
Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols are often lacking. Here, we describe the generation of clustered regularly-interspaced short palindromic repeats(CRISPR)-Cas9 engineered reporter knock-in embryonic stem cell lines in which tdTomato and a unique cell-surface protein, THY1.2, are expressed under the control of the retinal ganglion cell (RGC)-enriched gene BRN3B. Using these reporter cell lines, we greatly improved adherent stem cell differentiation to the RGC lineage by optimizing a novel combination of small molecules and established an anti-THY1.2-based protocol that allows for large-scale RGC immunopurification. RNA-sequencing confirmed the similarity of the stem cell-derived RGCs to their endogenous human counterparts. Additionally, we developed an in vitro axonal injury model suitable for studying signaling pathways and mechanisms of human RGC cell death and for high-throughput screening for neuroprotective compounds. Using this system in combination with RNAi-based knockdown, we show that knockdown of dual leucine kinase (DLK) promotes survival of human RGCs, expanding to the human system prior reports that DLK inhibition is neuroprotective for murine RGCs. These improvements will facilitate the development and use of large-scale experimental paradigms that require numbers of pure RGCs that were not previously obtainable. Stem Cells Translational Medicine 2017;6:1972-1986. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
Penchaszadeh, Victor B.; Schuler-Faccini, Lavinia
2014-01-01
Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976–1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program “Reencontro”, which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind. PMID:24764764
Penchaszadeh, Victor B; Schuler-Faccini, Lavinia
2014-03-01
Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.
Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.
2015-01-01
Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950
Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G
2015-05-01
Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.
Trial and error: how the unclonable human mitochondrial genome was cloned in yeast.
Bigger, Brian W; Liao, Ai-Yin; Sergijenko, Ana; Coutelle, Charles
2011-11-01
Development of a human mitochondrial gene delivery vector is a critical step in the ability to treat diseases arising from mutations in mitochondrial DNA. Although we have previously cloned the mouse mitochondrial genome in its entirety and developed it as a mitochondrial gene therapy vector, the human mitochondrial genome has been dubbed unclonable in E. coli, due to regions of instability in the D-loop and tRNA(Thr) gene. We tested multi- and single-copy vector systems for cloning human mitochondrial DNA in E. coli and Saccharomyces cerevisiae, including transformation-associated recombination. Human mitochondrial DNA is unclonable in E. coli and cannot be retained in multi- or single-copy vectors under any conditions. It was, however, possible to clone and stably maintain the entire human mitochondrial genome in yeast as long as a single-copy centromeric plasmid was used. D-loop and tRNA(Thr) were both stable and unmutated. This is the first report of cloning the entire human mitochondrial genome and the first step in developing a gene delivery vehicle for human mitochondrial gene therapy.
Reduced Pressure Cabin Testing of the Orion Atmosphere Revitalization Technology
NASA Technical Reports Server (NTRS)
Button, Amy; Sweterlitsch, Jeffrey
2011-01-01
An amine-based carbon dioxide (CO2) and water vapor sorbent in pressure-swing regenerable beds has been developed by Hamilton Sundstrand and baselined for the Atmosphere Revitalization System for moderate duration missions of the Orion Multipurpose Crew Vehicle. In previous years at this conference, reports were presented on extensive Johnson Space Center testing of this technology in a sea-level pressure environment with simulated and actual human metabolic loads in both open and closed-loop configurations. In 2011, the technology was tested in an open cabin-loop configuration at ambient and two sub-ambient pressures to compare the performance of the system to the results of previous tests at ambient pressure. The testing used a human metabolic simulator with a different type of water vapor generation than previously used, which added some unique challenges in the data analysis. This paper summarizes the results of: baseline and some matrix testing at all three cabin pressures, increased vacuum regeneration line pressure with a high metabolic load, a set of tests studying CO2 and water vapor co-adsorption effects relative to model-predicted performance, and validation tests of flight program computer model predictions with specific operating conditions.
Reduced Pressure Cabin Testing of the Orion Atmosphere Revitalization Technology
NASA Technical Reports Server (NTRS)
Button, Amy; Sweterlisch, Jeffery J.
2013-01-01
An amine-based carbon dioxide (CO2) and water vapor sorbent in pressure-swing regenerable beds has been developed by Hamilton Sundstrand and baselined for the Atmosphere Revitalization System for moderate duration missions of the Orion Multipurpose Crew Vehicle. In previous years at this conference, reports were presented on extensive Johnson Space Center testing of this technology in a sea-level pressure environment with simulated and actual human metabolic loads in both open and closed-loop configurations. In 2011, the technology was tested in an open cabin-loop configuration at ambient and two sub-ambient pressures to compare the performance of the system to the results of previous tests at ambient pressure. The testing used a human metabolic simulator with a different type of water vapor generation than previously used, which added some unique challenges in the data analysis. This paper summarizes the results of: baseline and some matrix testing at all three cabin pressures, increased vacuum regeneration line pressure with a high metabolic load, a set of tests studying CO2 and water vapor co-adsorption effects relative to model-predicted performance, and validation tests of flight program computer model predictions with specific operating conditions.
Reduced Pressure Cabin Testing of the Orion Atmosphere Revitalization Technology
NASA Technical Reports Server (NTRS)
Button, Amy B.; Sweterlitsch, Jeffrey J.
2013-01-01
An amine-based carbon dioxide (CO2) and water vapor sorbent in pressure-swing regenerable beds has been developed by United Technologies Corp. Aerospace Systems (UTAS, formerly Hamilton Sundstrand) and baselined for the Atmosphere Revitalization System for moderate duration missions of the Orion Multipurpose Crew Vehicle (MPCV). In previous years at this conference, reports were presented on extensive Johnson Space Center testing of this technology in a sea-level pressure environment with simulated and actual human metabolic loads in both open and closed-loop configurations. In 2011, the technology was tested in an open cabin-loop configuration at ambient and two sub-ambient pressures to compare the performance of the system to the results of previous tests at ambient pressure. The testing used a human metabolic simulator with a different type of water vapor generation than previously used, which added some unique challenges in the data analysis. This paper summarizes the results of: baseline and some matrix testing at all three cabin pressures, increased vacuum regeneration line pressure testing with a high metabolic load, a set of tests studying CO2 and water vapor co-adsorption effects relative to model-predicted performance, and validation tests of flight project computer model predictions with specific operating conditions.
Self-reported HIV antibody testing among Latino urban day laborers.
Solorio, Maria Rosa; Galvan, Frank H
2009-12-01
To identify the characteristics of male Latino urban day laborers who self-report having tested for human immunodeficiency virus (HIV). A cross-sectional survey was conducted with 356 Latino day laborers, aged 18 to 40 years, who had been sexually active in the previous 12 months, from 6 day labor sites in the City of Los Angeles. Most of the men were single, mainly from Mexico and Guatemala, and had been employed as a day laborer for fewer than 3 years; 38% had an annual income of $4000 or less. Ninety-two percent of the men reported having sex with women only, and 8% reported a history of having sex with men and women. Forty-six percent had received an HIV test in the previous 12 months and 1 person tested positive. In univariate logistic regression analyses, day laborers who were aged 26 years or older, had more than 3 years in the United States, had more than 1 year but fewer than 5 years employed as a day laborer, and had annual incomes greater than $4000 were significantly more likely to self-report HIV testing in the previous 12 months. In a multivariate logistic regression analysis, only higher annual income was found to be significantly associated with self-reported HIV testing. Interventions that target lower-income Latino day laborers are needed to promote early HIV detection. HIV detection offers individual benefits through treatment, with decreased morbidity and mortality, as well as public health benefits through decreased rates of HIV transmission in the community.
Cunningham, Andrew A.; Langton, Tom E. S.
2016-01-01
There have been few reconstructions of wildlife disease emergences, despite their extensive impact on biodiversity and human health. This is in large part attributable to the lack of structured and robust spatio-temporal datasets. We overcame logistical problems of obtaining suitable information by using data from a citizen science project and formulating spatio-temporal models of the spread of a wildlife pathogen (genus Ranavirus, infecting amphibians). We evaluated three main hypotheses for the rapid increase in disease reports in the UK: that outbreaks were being reported more frequently, that climate change had altered the interaction between hosts and a previously widespread pathogen, and that disease was emerging due to spatial spread of a novel pathogen. Our analysis characterized localized spread from nearby ponds, consistent with amphibian dispersal, but also revealed a highly significant trend for elevated rates of additional outbreaks in localities with higher human population density—pointing to human activities in also spreading the virus. Phylogenetic analyses of pathogen genomes support the inference of at least two independent introductions into the UK. Together these results point strongly to humans repeatedly translocating ranaviruses into the UK from other countries and between UK ponds, and therefore suggest potential control measures. PMID:27683363
Acute optic nerve sheath fenestration in humans using the free electron laser (FEL): a case report
NASA Astrophysics Data System (ADS)
Joos, Karen M.; Mawn, Louise A.; Shen, Jin-Hui; Jansen, E. Duco; Casagrande, Vivien A.
2002-06-01
Our previous studies using rabbits and monkeys showed that the Amide II wavelength (6.45 micrometers ) produced by the FEL could efficiently produce an optic nerve sheath fenestration with minimal damage. In order to determine if the technology safely could be applied to human surgery, we used 2 blind human eyes during enucleation to compare the results of producing fenestrations with the FEL or a scissors. FDA and Vanderbilt IRB approvals, and individual patient consents were obtained. The FEL energy was transmitted to a human operating room. After disinsertion of the medial rectus muscle, an optic nerve sheath fenestration (2 mm diameter) was made with either the FEL (6.45 micrometers , 325 micrometers spot size, 30 Hz, 3 mJ) through a hollow waveguide surgical probe or with a scissors. The enucleation was then completed. The optic nerve was dissected from the globe and fixed. Specimens were examined histologically. Dural incisions were effective with both methods. FEL energy at 6.45 micrometers can be transmitted to an operating room and delivered to human ocular tissue through a hollow waveguide surgical probe. This FEL wavelength can produce an optic nerve sheath fenestration without acute direct damage to the nerve in this case report.
Al-Tawfiq, Jaffar A; Laxminarayan, Ramanan; Mendelson, Marc
2017-01-01
The widespread use of antibiotics in humans and animals has contributed to growing rates of antibiotic resistance. Previously treatable bacterial infections now require the last line of antibiotics or are untreatable. The current antibiotic of last resort for carbapenem-resistant Gram-negative bacterial infections is often colistin. Evidence for the shifting pattern of colistin resistance and how the international community should respond are discussed in this review. The literature on colistin resistance was reviewed. Plasmid-mediated colistin resistance encoded by mcr-1 was first documented in China during the routine surveillance of food animals. This has been followed by similar reports across a wide geographic area, in humans, animals, and the environment. The mcr-1 gene has been reported among human isolates in 29 countries, related to environmental samples in four countries, and in food animals and other animals in 28 countries. More recently, a second gene encoding resistance, mcr-2, has been isolated from porcine and bovine Escherichia coli. The emergence and horizontal transmission of colistin resistance highlights the need for heightened stewardship efforts across the One Health platform for this antibiotic of last resort, and indeed for all antibiotics used in animals and humans. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Kishore, Vipuil; Bullock, Whitney; Sun, Xuanhao; Van Dyke, William Scott; Akkus, Ozan
2011-01-01
Topographical cues from the extracellular microenvironment can influence cellular activity including proliferation and differentiation. Information on the effects of material topography on tenogenic differentiation of human mesenchymal stem cells (human MSCs) is limited. A methodology using the principles of isoelectric focusing has previously been developed in our laboratory to synthesize electrochemically aligned collagen (ELAC) threads that mimics the packing density, alignment and strength of collagen dense connective tissues. In the current study, human MSCs were cultured on ELAC and randomly-oriented collagen threads and the effect of collagen orientation on cell morphology, proliferation and tenogenic differentiation was investigated. The results indicate that higher rates of proliferation were observed on randomly oriented collagen threads compared to ELAC threads. On the other hand, tendon specific markers such as scleraxis, tenomodulin, tenascin-C and collagen-III were significantly increased on ELAC threads compared to randomly oriented collagen threads. Additionally, osteocalcin, a specific marker of bone differentiation was suppressed on ELAC threads. Previous studies have reported that BMP-12 is a key growth factor to induce tenogenic differentiation of human MSCs. To evaluate the synergistic effect of BMP-12 and collagen orientation, human MSCs were cultured on ELAC threads in culture medium supplemented with and without BMP-12. The results revealed that BMP-12 did not have an additional effect on the tenogenic differentiation of human MSCs on ELAC threads. Together, these results suggest that ELAC induces tenogenic differentiation of human MSCs by presenting an aligned and dense collagen substrate, akin to the tendon itself. In conclusion, ELAC has a significant potential to be used as a tendon replacement and in the development of an osteotendinous construct towards the regeneration of bone-tendon interfaces. PMID:22177622
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lane, R.P.; Vielmetter, J.; Dreyer, W.J.
1996-08-01
The neuronal cell adhesion molecule Bravo/Nr-CAM is a cell surface protein of the immunoglobulin (Ig) superfamily and is closely related to the L1/NgCAM and neurofascin molecules, all of which contain six immunoglobulin domains, five fibronectin repeats, a transmembrane region, and an intracellular domain. Chicken Bravo/Nr-CAM has been shown to interact with other cell surface molecules of the Ig superfamily and has been implicated in specific pathfinding roles of axonal growth cones in the developing nervous system. We now report the characterization of cDNA clones encoding the human Bravo/Nr-CAM protein, which, like its chicken homolog, is composed of six V-like Igmore » domains and five fibronectin type III repeats. The human Bravo/Nr-CAM homolog also contains a transmembrane and intracellular domain, both of which are 100% conserved at the amino acid level compared to its chicken homolog. Overall, the human Bravo/Nr-CAM homolog is 82% identical to the chicken Bravo/Nr-CAM amino acid sequence. Independent cDNAs encoding four different isoforms were also identified, all of which contain alternatively spliced variants around the fifth fibronectin type III repeat, including one isoform that had been previously identified for chicken Bravo/Nr-CAM. Northern blot analysis reveals one mRNA species of approximately 7.0 kb in adult human brain tissue. Fluorescence in situ hybridization maps the gene for human Bravo/Nr-CAM to human chromosome 7q31.1-q31.2. This chromosomal locus has been previously identified as containing a tumore suppressor candidate gene commonly deleted in certain human cancer tissues. 38 refs., 5 figs.« less
Oudni-M'rad, Myriam; M'rad, Selim; Ksia, Amine; Lamiri, Rachida; Mekki, Mongi; Nouri, Abdellatif; Mezhoud, Habib; Babba, Hamouda
2016-03-01
Cystic echinococcosis is a widespread zoonotic parasitic disease especially in Tunisia which is one of the most endemic countries in the Mediterranean area. The etiological agent, Echinococcus granulosus sensu lato, implies dogs and other canids as definitive hosts and different herbivore species as intermediate hosts. Human contamination occurs during the consumption of parasite eggs passed in the environment through canid feces. Hydatid cysts coming from a child operated for multiple echinococcosis were collected and analyzed in order to genotype and to obtain some epidemiological molecular information. Three targets, ribosomal DNA ITS1 fragment, NADH dehydrogenase subunit 1 (nad1), and mitochondrial cytochrome c oxydase subunit 1 (CO1) genes, were amplified and analyzed by RFLP and sequencing approach. This study presents the first worldwide report in human of a simultaneous infection with Echinococcus granulosus sensu stricto (genotype G1) and Echinococcus canadensis (genotype G6) species. This is also the first report of the presence of E. canadensis in the Tunisian population which argues in favor of a greater importance of this species in human infestation in Tunisia than previously believed.
Immune Reconstitution Reactions in Human Immunodeficiency Virus–Negative Patients
Scharschmidt, Tiffany C.; Amerson, Erin H.; Rosenberg, Oren S.; Jacobs, Richard A.; McCalmont, Timothy H.; Shinkai, Kanade
2013-01-01
Background Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon initially described in patients with human immunodeficiency virus. Upon initiation of combination antiretroviral therapy, recovery of cellular immunity triggers inflammation to a preexisting infection or antigen that causes paradoxical worsening of clinical disease. A similar phenomenon can occur in human immunodeficiency virus–negative patients, including pregnant women, neutropenic hosts, solidorgan or stem cell transplant recipients, and patients receiving tumor necrosis factor inhibitors. Observations We report a case of leprosy unmasking and downgrading reaction after stem cell transplantation that highlights some of the challenges inherent to the diagnosis of IRIS, especially in patients without human immunodeficiency virus infection, as well as review the spectrum of previously reported cases of IRIS reactions in this population. Conclusions The mechanism of immune reconstitution reactions is complex and variable, depending on the underlying antigen and the mechanism of immunosuppression or shift in immune status. Use of the term IRIS can aid our recognition of an important phenomenon that occurs in the setting of immunosuppression or shifts in immunity but should not deter us from thinking critically about the distinct processes that underlie this heterogeneous group of conditions. PMID:23324760
The Interaction of Anti-diabetic α-Glucosidase Inhibitors and Gut Bacteria α-Glucosidase.
Tan, Kemin; Tesar, Christine; Wilton, Rosemarie; Jedrzejczak, Robert P; Joachimiak, Andrzej
2018-05-15
Carbohydrate hydrolyzing α-glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an α-glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro-αG1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro-αG1 homologs among other species that colonize the human gut. In this report, we present structures of Ro-αG1 in complex with the anti-diabetic α-glucosidase inhibitors voglibose, miglitol and acarbose and supporting binding data. The in vitro binding of these anti-diabetic drugs to Ro-αG1 suggests the potential for unintended in vivo cross-reaction of the α-glucosidase inhibitors to bacterial α-glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug-bound enzyme structures could benefit further anti-diabetic drug development. This article is protected by copyright. All rights reserved. © 2018 The Protein Society.
Johnson, Darryl; Carter, Melissa D; Crow, Brian S; Isenberg, Samantha L; Graham, Leigh Ann; Erol, H Akin; Watson, Caroline M; Pantazides, Brooke G; van der Schans, Marcel J; Langenberg, Jan P; Noort, Daan; Blake, Thomas A; Thomas, Jerry D; Johnson, Rudolph C
2015-04-01
Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to form the aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic-UHPLC-MS/MS method for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. The method has a reportable range from 2.0 ng/ml to 150 ng/ml, which is consistent with the sensitivity of methods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥85%) and precision (RSD ≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72 h at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20 and demonstrates a threefold improvement in sensitivity. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Walter, Kyla M; Lin, Yan-Ping; Kass, Philip H; Puschner, Birgit
2017-05-03
Hyperthyroidism is the most common endocrine disorder observed in domestic felines; however, its etiology is largely unknown. Two classes of persistent organic pollutants, polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are known to interfere with thyroid hormone (TH) signaling and regulation; thus, it is postulated that they contribute to the etiopathogenesis of feline hyperthyroidism and pose a risk to humans and other species. In this case-control study, the concentrations of 13 PBDE and 11 PCB congeners were measured by gas chromatography mass spectrometry in serum or plasma samples from 20 hyperthyroid and 31 control cats in order to investigate the association between concentration of PBDE and PCB congeners and feline hyperthyroidism. Logistic regression analysis was used to determine whether elevated concentrations of individual congeners were associated with a higher risk of feline hyperthyroidism. Hyperthyroid cats had higher concentrations of four PBDE congeners (BDE17, BDE100, BDE47, and BDE49) and five PCB congeners (PCB131, PCB153, PCB174, PCB180, and PCB196), compared to control cats. In addition, the sum of both PBDE and PCB congener concentrations were elevated in the hyperthyroid group compared to control cats; however, only the increased PCB concentrations were statistically significant. The sum total PBDE concentrations in our feline samples were approximately 50 times greater than concentrations previously reported in human populations from a geographically similar area, whereas sum total PCB concentrations were comparable to those previously reported in humans. These observational findings support the hypothesis that PBDEs and PCBs may contribute to the etiopathogenesis of hyperthyroidism in felines. As domestic house cats are often exposed to higher concentrations of PBDEs than humans, they may serve as sentinels for the risk of TH disruption that these pollutants pose to humans and other species.
Human Geophagia, Calabash Chalk and Undongo: Mineral Element Nutritional Implications
Abrahams, Peter W.; Davies, Theo C.; Solomon, Abiye O.; Trow, Amanda J.; Wragg, Joanna
2013-01-01
The prime aim of our work is to report and comment on the bioaccessible concentrations – i.e., the soluble content of chemical elements in the gastrointestinal environment that is available for absorption – of a number of essential mineral nutrients and potentially harmful elements (PHEs) associated with the deliberate ingestion of African geophagical materials, namely Calabash chalk and Undongo. The pseudo-total concentrations of 13 mineral nutrients/PHEs were quantified following a nitric-perchloric acid digestion of nine different Calabash chalk samples, and bioaccessible contents of eight of these chemical elements were determined in simulated saliva/gastric and intestinal solutions obtained via use of the Fed ORganic Estimation human Simulation Test (FOREhST) in vitro procedure. The Calabash chalk pseudo-total content of the chemical elements is often below what may be regarded as average for soils/shales, and no concentration is excessively high. The in vitro leachate solutions had concentrations that were often lower than those of the blanks used in our experimental procedure, indicative of effective adsorption: lead, a PHE about which concern has been previously raised in connection with the consumption of Calabash chalk, was one such chemical element where this was evident. However, some concentrations in the leachate solutions are suggestive that Calabash chalk can be a source of chemical elements to humans in bioaccessible form, although generally the materials appear to be only a modest supplier: this applies even to iron, a mineral nutrient that has often been linked to the benefits of geophagia in previous academic literature. Our investigations indicate that at the reported rates of ingestion, Calabash chalk on the whole is not an important source of mineral nutrients or PHEs to humans. Similarly, although Undongo contains elevated pseudo-total concentrations of chromium and nickel, this soil is not a significant source to humans for any of the bioaccessible elements investigated. PMID:23308189
Human geophagia, calabash chalk and undongo: mineral element nutritional implications.
Abrahams, Peter W; Davies, Theo C; Solomon, Abiye O; Trow, Amanda J; Wragg, Joanna
2013-01-01
The prime aim of our work is to report and comment on the bioaccessible concentrations - i.e., the soluble content of chemical elements in the gastrointestinal environment that is available for absorption - of a number of essential mineral nutrients and potentially harmful elements (PHEs) associated with the deliberate ingestion of African geophagical materials, namely Calabash chalk and Undongo. The pseudo-total concentrations of 13 mineral nutrients/PHEs were quantified following a nitric-perchloric acid digestion of nine different Calabash chalk samples, and bioaccessible contents of eight of these chemical elements were determined in simulated saliva/gastric and intestinal solutions obtained via use of the Fed ORganic Estimation human Simulation Test (FOREhST) in vitro procedure. The Calabash chalk pseudo-total content of the chemical elements is often below what may be regarded as average for soils/shales, and no concentration is excessively high. The in vitro leachate solutions had concentrations that were often lower than those of the blanks used in our experimental procedure, indicative of effective adsorption: lead, a PHE about which concern has been previously raised in connection with the consumption of Calabash chalk, was one such chemical element where this was evident. However, some concentrations in the leachate solutions are suggestive that Calabash chalk can be a source of chemical elements to humans in bioaccessible form, although generally the materials appear to be only a modest supplier: this applies even to iron, a mineral nutrient that has often been linked to the benefits of geophagia in previous academic literature. Our investigations indicate that at the reported rates of ingestion, Calabash chalk on the whole is not an important source of mineral nutrients or PHEs to humans. Similarly, although Undongo contains elevated pseudo-total concentrations of chromium and nickel, this soil is not a significant source to humans for any of the bioaccessible elements investigated.
Smith, Sherri A; Gagnon, Sandra; Waters, Nigel J
2017-03-01
1. The plasma clearance of the first-in-class DOT1L inhibitor, EPZ-5676 (pinometostat), was shown to be markedly lower in human compared to the preclinical species, mouse, rat and dog. 2. This led to vertical allometry where various interspecies scaling methods were applied to the data, with fold-errors between 4 and 13. We had previously reported the elimination and metabolic pathways of EPZ-5676 were similar across species. Therefore, the aim of this work was to explore the mechanistic basis for the species difference in clearance for EPZ-5676, focusing on other aspects of disposition. 3. The protein binding of EPZ-5676 in human plasma demonstrated a non-linear relationship suggesting saturable binding at physiologically relevant concentrations. Saturation of protein binding was not observed in plasma from preclinical species. Kinetic determinations using purified serum albumin and alpha-1-acid glycoprotein (AAG) confirmed that EPZ-5676 is a high affinity ligand for AAG with a dissociation constant (K d ) of 0.24 μM. 4. Permeability limited uptake was also considered since hepatocyte CL int was much lower in human relative to preclinical species. Passive unbound CL int for EPZ-5676 was estimated using a correlation analysis of logD and data previously reported on seven drugs in sandwich cultured human hepatocytes. 5. Incorporation of AAG binding and permeability limited hepatic uptake into the well-stirred liver model gave rise to a predicted clearance for EPZ-5676 within 2-fold of the observed value of 1.4 mL min -1 kg -1 . This analysis suggests that the marked species difference in EPZ-5676 clearance is driven by high affinity binding to human AAG as well as species-specific hepatic uptake invoking the role of transporters.
Auditory Contagious Yawning in Humans: An Investigation into Affiliation and Status Effects
Massen, Jorg J. M.; Church, Allyson M.; Gallup, Andrew C.
2015-01-01
While comparative research on contagious yawning has grown substantially in the past few years, both the interpersonal factors influencing this response and the sensory modalities involved in its activation in humans remain relatively unknown. Extending upon previous studies showing various in-group and status effects in non-human great apes, we performed an initial study to investigate how the political affiliation (Democrat vs. Republican) and status (high vs. low) of target stimuli influences auditory contagious yawning, as well as the urge to yawn, in humans. Self-report responses and a subset of video recordings were analyzed from 118 undergraduate students in the US following exposure to either breathing (control) or yawning (experimental) vocalizations paired with images of former US Presidents (high status) and their respective Cabinet Secretaries of Commerce (low status). The overall results validate the use of auditory stimuli to prompt yawn contagion, with greater response in the experimental than the control condition. There was also a negative effect of political status on self-reported yawning and the self-reported urge to yawn irrespective of the condition. In contrast, we found no evidence for a political affiliation bias in this response. These preliminary findings are discussed in terms of the existing comparative evidence, though we highlight limitations in the current investigation and we provide suggestions for future research in this area. PMID:26617557
ERIC Educational Resources Information Center
Song, Yan; Li, Xiaoming; Zhang, Liying; Liu, Yingjie; Jiang, Shulin; Stanton, Bonita
2012-01-01
Background: Sexually-transmitted disease (STD) is a facilitating cofactor that contributes to human immunodeficiency virus (HIV) transmission. Previous studies indicated a high prevalence of STDs among men who have sex with men (MSM) in China. To date, limited data are available for correlates of STD infection among young migrant MSM in China. The…
ERIC Educational Resources Information Center
Jax, Steven A.; Rosenbaum, David A.
2007-01-01
According to a prominent theory of human perception and performance (M. A. Goodale & A. D. Milner, 1992), the dorsal, action-related stream only controls visually guided actions in real time. Such a system would be predicted to show little or no action priming from previous experience. The 3 experiments reported here were designed to determine…
The Geology of Somalia: A Selected Bibliography of Somalian Geology, Geography and Earth Science
2007-02-01
31, Issue 6, Pages 302-307. Descriptors: Child, Preschool; Developing Countries; English Abstract; Humans; Nutritional Status; Primary Health Care...much smaller figures than had been reported previously. Data on the nutritional status of all children under 5 was collected at the vaccination places...gypsum beds underlying the compact sedimentary formations capping the hills. ISSN: 0365-7477. Centers for Disease Control (CDC). 1989. “ Nutritional
Avian schistosomes and outbreaks of cercarial dermatitis.
Horák, Petr; Mikeš, Libor; Lichtenbergová, Lucie; Skála, Vladimír; Soldánová, Miroslava; Brant, Sara Vanessa
2015-01-01
Cercarial dermatitis (swimmer's itch) is a condition caused by infective larvae (cercariae) of a species-rich group of mammalian and avian schistosomes. Over the last decade, it has been reported in areas that previously had few or no cases of dermatitis and is thus considered an emerging disease. It is obvious that avian schistosomes are responsible for the majority of reported dermatitis outbreaks around the world, and thus they are the primary focus of this review. Although they infect humans, they do not mature and usually die in the skin. Experimental infections of avian schistosomes in mice show that in previously exposed hosts, there is a strong skin immune reaction that kills the schistosome. However, penetration of larvae into naive mice can result in temporary migration from the skin. This is of particular interest because the worms are able to migrate to different organs, for example, the lungs in the case of visceral schistosomes and the central nervous system in the case of nasal schistosomes. The risk of such migration and accompanying disorders needs to be clarified for humans and animals of interest (e.g., dogs). Herein we compiled the most comprehensive review of the diversity, immunology, and epidemiology of avian schistosomes causing cercarial dermatitis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Badr, Eman; ElHefnawi, Mahmoud; Heath, Lenwood S
2016-01-01
Alternative splicing is a vital process for regulating gene expression and promoting proteomic diversity. It plays a key role in tissue-specific expressed genes. This specificity is mainly regulated by splicing factors that bind to specific sequences called splicing regulatory elements (SREs). Here, we report a genome-wide analysis to study alternative splicing on multiple tissues, including brain, heart, liver, and muscle. We propose a pipeline to identify differential exons across tissues and hence tissue-specific SREs. In our pipeline, we utilize the DEXSeq package along with our previously reported algorithms. Utilizing the publicly available RNA-Seq data set from the Human BodyMap project, we identified 28,100 differentially used exons across the four tissues. We identified tissue-specific exonic splicing enhancers that overlap with various previously published experimental and computational databases. A complicated exonic enhancer regulatory network was revealed, where multiple exonic enhancers were found across multiple tissues while some were found only in specific tissues. Putative combinatorial exonic enhancers and silencers were discovered as well, which may be responsible for exon inclusion or exclusion across tissues. Some of the exonic enhancers are found to be co-occurring with multiple exonic silencers and vice versa, which demonstrates a complicated relationship between tissue-specific exonic enhancers and silencers.
Ariza-Miguel, Jaime; Fernández-Natal, María Isabel; Soriano, Francisco; Hernández, Marta; Stessl, Beatrix; Rodríguez-Lázaro, David
2015-01-01
We investigated the pathogenicity, invasiveness, and genetic relatedness of 17 clinical Listeria monocytogenes stains isolated over a period of nine years (2006-2014). All isolates were phenotypically characterised and growth patterns were determined. The antimicrobial susceptibility of L. monocytogenes isolates was determined in E-tests. Invasion assays were performed with epithelial HeLa cells. Finally, L. monocytogenes isolates were subtyped by PFGE and MLST. All isolates had similar phenotypic characteristics (β-haemolysis and lecithinase activity), and three types of growth curve were observed. Bacterial recovery rates after invasion assays ranged from 0.09% to 7.26% (1.62 ± 0.46). MLST identified 11 sequence types (STs), and 14 PFGE profiles were obtained, indicating a high degree of genetic diversity. Genetic studies unequivocally revealed the occurrence of one outbreak of listeriosis in humans that had not previously been reported. This outbreak occurred in October 2009 and affected three patients from neighbouring towns. In conclusion, the molecular epidemiological analysis clearly revealed a cluster (three human cases, all ST1) of not previously reported listeriosis cases in northwestern Spain. Our findings indicate that molecular subtyping, in combination with epidemiological case analysis, is essential and should be implemented in routine diagnosis, to improve the tracing of the sources of outbreaks.
Biaxial Response of Passive Human Cerebral Arteries
Monson, Kenneth L.; Barbaro, Nicholas M.; Manley, Geoffrey T.
2008-01-01
The cerebral circulation is fundamental to the health and maintenance of brain tissue, but injury and disease may result in dysfunction of the vessels. Characterization of cerebral vessel mechanical response is an important step toward a more complete understanding of injury mechanisms and disease development in these vessels, paving the way for improved prevention and treatment. We recently reported a large series of uniaxial tests on fresh human cerebral vessels, but the multi-axial behavior of these vessels has not been previously described. Twelve arteries were obtained from the surface of the temporal lobe of patients undergoing surgery and were subjected to various combinations of axial stretch and pressure around typical physiological conditions before being stretched to failure. Axial and circumferential responses were compared, and measured data were fit to a four parameter, Fung-type hyperelastic constitutive model. Artery behavior was nonlinear and anisotropic, with considerably greater resistance to deformation in the axial direction than around the circumference. Results from axial failure tests of pressurized vessels resulted in a small shift in stress-stretch response compared to previously reported data from unpressurized specimens. These results further define the biaxial response of the cerebral arteries and provide data required for more rigorous study of head injury mechanisms and development of cerebrovascular disease. PMID:18855141
Ta, Tang Thuy-Huong; Salas, Ana; Ali-Tammam, Marwa; Martínez, María Del Carmen; Lanza, Marta; Arroyo, Eduardo; Rubio, Jose Miguel
2010-07-27
Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia. A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009. His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment. Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative. This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported. Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006. Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia. This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection. Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very young children under five years old.
2010-01-01
Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia. A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009. His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment. Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative. This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported. Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006. Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia. This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection. Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very young children under five years old. PMID:20663184
Characterization of rabies virus from a human case in Nepal.
Pant, G R; Horton, D L; Dahal, M; Rai, J N; Ide, S; Leech, S; Marston, D A; McElhinney, L M; Fooks, A R
2011-04-01
Rabies is endemic throughout most of Asia, with the majority of human cases transmitted by domestic dogs (Canis familiaris). Here, we report a case of rabies in a 12-year-old girl in the Lalitpur district of Nepal that might have been prevented by better public awareness and timely post-exposure prophylaxis. Molecular characterization of the virus showed 100% identity over a partial nucleoprotein gene sequence to previous isolates from Nepal belonging to the 'arctic-like' lineage of rabies virus. Sequence analysis of both partial nucleoprotein and glycoprotein genes showed differences in consensus sequence after passage in vitro but not after passage in vivo.
Khanal, Neelam; Masellis, Chiara; Kamrath, Michael Z; Clemmer, David E; Rizzo, Thomas R
2018-04-16
We report here our combination of cryogenic, messenger-tagging, infrared (IR) spectroscopy with ion mobility spectrometry (IMS) and mass spectrometry (MS) as a way to identify and analyze a set of human milk oligosaccharides (HMOs) ranging from trisaccharides to hexasaccharides. The added dimension of IR spectroscopy provides a diagnostic fingerprint in the OH and NH stretching region, which is crucial to identify these oligosaccharides, which are difficult to distinguish by IMS alone. These results extend our previous work in demonstrating the generality of this combined approach for distinguishing subtly different structural and regioisomers of glycans of biologically relevant size.
Chai, Chunxia; Wang, Qiao; Cao, Sanjie; Zhao, Qin; Wen, Yiping; Huang, Xiaobo; Wen, Xintian; Yan, Qiguai; Ma, Xiaoping; Wu, Rui
2018-01-31
Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic flavivirus causing viral encephalitis in humans and reproductive disorder in swine. JEV is prevalent throughout China in human; however, spatiotemporal analysis of JEV in Chinese swine herds has not been reported previously. Herein, we present serological and molecular epidemiological results and estimates of prevalence of JEV infections among swine herds in various regions of China. The results suggest that JEV infections are widespread and genotype I and III strains co-exist in the same regions. Therefore, there is an urgent need to monitor JEV infection status among swine herds in China.
Chai, Chunxia; Wang, Qiao; Cao, Sanjie; Zhao, Qin; Wen, Yiping; Huang, Xiaobo; Wen, Xintian; Yan, Qiguai; Ma, Xiaoping
2018-01-01
Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic flavivirus causing viral encephalitis in humans and reproductive disorder in swine. JEV is prevalent throughout China in human; however, spatiotemporal analysis of JEV in Chinese swine herds has not been reported previously. Herein, we present serological and molecular epidemiological results and estimates of prevalence of JEV infections among swine herds in various regions of China. The results suggest that JEV infections are widespread and genotype I and III strains co-exist in the same regions. Therefore, there is an urgent need to monitor JEV infection status among swine herds in China. PMID:28693301
[Does the right to die with dignity exist?].
Toro Flores, Rafael
2008-12-01
Death is one of the few certainties in human beings. This reality generates uneasiness regarding how death will occur especially in circumstances of loneliness or suffering which can become agony. In this report, the author first analyzes the existence of the right to die with dignity as a human right which takes on the nature of being a subjective right. In continuation, the author describes the existing problematic in the application of this right to die in relationship to the so-called double effect mechanism and euthanasia. The author concludes this article by proposing previous instructions or anticipated desires as ideal measures to make the right to die with dignity valid.
Clonorchis sinensis and Opisthorchis spp. in Vietnam: current status and prospects.
Doanh, Pham N; Nawa, Yukifumi
2016-01-01
Clonorchis sinensis and Opisthorchis viverrini are clinically important small liver flukes because of their known association with development of cholangiocarcinoma. In Vietnam, high prevalence of C. sinensis infection in humans was previously reported in northern provinces, and O. viverrini infection has been detected in several central provinces. However, diagnosis of C. sinensis and O. viverrini infections in the past was merely based on faecal egg examination. This method alone can lead to misidentification at the species level because of morphological similarity between the eggs of these liver flukes and minute intestinal trematodes of the family Heterophyidae. In fact, recent surveys in Vietnam revealed that infection with several minute intestinal flukes, such as Haplorchis pumilio and H. taichui, are much more common than infection with C. sinensis or O. viverrini, and they often co-infect humans. Thus, previously reported prevalence of small liver fluke infection in Vietnam was likely over-estimated due to mis identification of parasites in copro-parasitological examinations. In addition, there is some confusion about identification of cercariae, metacercariae and also adults of C. sinensis and O. viverrini in intermediate and definitive hosts. The aim of this review is, therefore, to draw realistic pictures of the past and present scientific reports on the epidemiology and biology of C. sinensis and Opisthorchis spp. infection in Vietnam. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Crawshaw, Ania A; Dhasmana, Divya; Jones, Brynmor; Gabriel, Carolyn M; Sturman, Steve; Davies, Nicholas W S; Taylor, Graham P
2018-04-01
Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) is well described. Clinical features are predominantly consistent with cord pathology, though imaging and autopsy studies also demonstrate brain inflammation. In general, this is subclinical; however, six cases have previously been reported of encephalopathy in HTLV-1-infected patients, without alternative identified aetiology. We describe three further cases of encephalitis in the UK HAM cohort (n = 142), whereas the annual incidence of acute encephalitis in the general population is 0.07-12.6 per 100,000. Clinical features included reduced consciousness, fever/hypothermia, headaches, seizures, and focal neurology. Investigation showed: raised CSF protein; pleocytosis; raised CSF:peripheral blood mononuclear cell HTLV-1 proviral load ratio; and MRI either normal or showing white matter changes in brain and cord. Four of the six previous case reports of encephalopathy in HTLV-infected patients also had HAM. Histopathology, reported in three, showed perivascular predominantly CD8+ lymphocytic infiltrates in the brain. One had cerebral demyelination, and all had cord demyelination. We have reviewed the existing six cases in the literature, together with our three new cases. In all seven with HAM, the spastic paraparesis deteriorated sub-acutely preceding encephalitis. Eight of the nine were female, and four of the seven treated with steroids improved. We propose that HTLV-associated encephalopathy may be part of the spectrum of HTLV-1-induced central nervous system disease.
Cutaneous Emergence of Eustrongylides in Two Persons from South Sudan
Eberhard, Mark L.; Ruiz-Tiben, Ernesto
2014-01-01
Two large, living worms were collected as they emerged from the lower limb of each of two persons in South Sudan. The worms were observed by staff of the South Sudan Guinea Worm Eradication Program during surveillance activities in communities at-risk for cases of Guinea worm disease (dracunculiasis). The worms measured 7 and 8 cm in length and were identified as fourth-stage larvae of Eustrongylides. This is the first report of such worms emerging from the skin; all five previous reports of human infection involved surgical removal of worms from the peritoneal cavity. PMID:24379241
Andes Virus and First Case Report of Bermejo Virus Causing Fatal Pulmonary Syndrome
Della Valle, Marcelo González; Alai, María Garcia; Cortada, Pedro; Villagra, Mario; Gianella, Alberto
2002-01-01
Two suspected hantavirus pulmonary syndrome (HPS) cases from Bolivia were confirmed by enzyme-linked immunosorbent assay. (ELISA)-ANDES was performed using N-Andes recombinant antigen serology in May and July 2000. Clot RNAs from the two patients were subjected to reverse transcription–polymerase chain reaction (PCR) amplification and sequencing. We describe two characterized cases of HPS. One was caused by infection with Bermejo virus and the other with Andes Nort viral lineage, both previously obtained from Oligoryzomys species. This is the first report of molecular identification of a human hantavirus associated with Bermejo virus. PMID:11971782
Acute Peritonitis Caused by Staphylococcus capitis in a Peritoneal Dialysis Patient.
Basic-Jukic, Nikolina
Acute peritonitis remains the most common complication of peritoneal dialysis (PD), with coagulase-negative staphylococci (CoNS) reported to account for more than 25% of peritonitis episodes (1). Staphylococcus capitis is a gram-positive, catalase-positive CoNS that was originally identified as a commensal on the skin of the human scalp (2). Advancement of microbiological technologies for bacterial identification enables diagnosis of previously unknown causes of acute peritonitis. This is the first reported case of acute peritonitis in a PD patient caused by S. capitis. Copyright © 2017 International Society for Peritoneal Dialysis.
Lactational mastitis caused by Streptococcus lactarius.
Tena, Daniel; Fernández, Cristina; López-Garrido, Beatriz; Pérez-Balsalobre, Mercedes; Losa, Cristina; Medina-Pascual, María José; Sáez-Nieto, Juan Antonio
2016-08-01
Human infections caused by Streptococcus lactarius have not been previously reported. In the present report, we describe a lactational mastitis caused by this organism. The infection occurred in a 28-year-old breast-feeding female, with a 10-days history of moderate pain on the right breast. The patient was cured after antibiotic treatment with levofloxacin for 21 days. Our case shows that S. lactarius should be considered as a cause of lactational mastitis. The introduction of molecular microbiology techniques can be extremely useful for knowing the implication of streptococci in lactational mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.
Gledhill, Karl; Guo, Zongyou; Umegaki-Arao, Noriko; Higgins, Claire A.; Itoh, Munenari; Christiano, Angela M.
2015-01-01
The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes. PMID:26308443
Yasukawa, Keiko; Shimosawa, Tatsuo; Okubo, Shigeo; Yatomi, Yutaka
2018-01-01
Background Human mercaptalbumin and human non-mercaptalbumin have been reported as markers for various pathological conditions, such as kidney and liver diseases. These markers play important roles in redox regulations throughout the body. Despite the recognition of these markers in various pathophysiologic conditions, the measurements of human mercaptalbumin and non-mercaptalbumin have not been popular because of the technical complexity and long measurement time of conventional methods. Methods Based on previous reports, we explored the optimal analytical conditions for a high-performance liquid chromatography method using an anion-exchange column packed with a hydrophilic polyvinyl alcohol gel. The method was then validated using performance tests as well as measurements of various patients' serum samples. Results We successfully established a reliable high-performance liquid chromatography method with an analytical time of only 12 min per test. The repeatability (within-day variability) and reproducibility (day-to-day variability) were 0.30% and 0.27% (CV), respectively. A very good correlation was obtained with the results of the conventional method. Conclusions A practical method for the clinical measurement of human mercaptalbumin and non-mercaptalbumin was established. This high-performance liquid chromatography method is expected to be a powerful tool enabling the expansion of clinical usefulness and ensuring the elucidation of the roles of albumin in redox reactions throughout the human body.
Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong
2016-08-03
Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.
Friedman, Melissa A; Fernandez, Mercedes; Backer, Lorraine C; Dickey, Robert W; Bernstein, Jeffrey; Schrank, Kathleen; Kibler, Steven; Stephan, Wendy; Gribble, Matthew O; Bienfang, Paul; Bowen, Robert E; Degrasse, Stacey; Flores Quintana, Harold A; Loeffler, Christopher R; Weisman, Richard; Blythe, Donna; Berdalet, Elisa; Ayyar, Ram; Clarkson-Townsend, Danielle; Swajian, Karen; Benner, Ronald; Brewer, Tom; Fleming, Lora E
2017-03-14
Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties.
Friedman, Melissa A.; Fernandez, Mercedes; Backer, Lorraine C.; Dickey, Robert W.; Bernstein, Jeffrey; Schrank, Kathleen; Kibler, Steven; Stephan, Wendy; Gribble, Matthew O.; Bienfang, Paul; Bowen, Robert E.; Degrasse, Stacey; Flores Quintana, Harold A.; Loeffler, Christopher R.; Weisman, Richard; Blythe, Donna; Berdalet, Elisa; Ayyar, Ram; Clarkson-Townsend, Danielle; Swajian, Karen; Benner, Ronald; Brewer, Tom; Fleming, Lora E.
2017-01-01
Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties. PMID:28335428
Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression.
Karlsson, Asa; Deb-Basu, Debabrita; Cherry, Athena; Turner, Stephanie; Ford, James; Felsher, Dean W
2003-08-19
DNA repair mechanisms are essential for the maintenance of genomic integrity. Disruption of gene products responsible for DNA repair can result in chromosomal damage. Improperly repaired chromosomal damage can result in the loss of chromosomes or the generation of chromosomal deletions or translocations, which can lead to tumorigenesis. The MYC protooncogene is a transcription factor whose overexpression is frequently associated with human neoplasia. MYC has not been previously implicated in a role in DNA repair. Here we report that the overexpression of MYC disrupts the repair of double-strand DNA breaks, resulting in a several-magnitude increase in chromosomal breaks and translocations. We found that MYC inhibited the repair of gamma irradiation DNA breaks in normal human cells and blocked the repair of a single double-strand break engineered to occur in an immortal cell line. By spectral karyotypic analysis, we found that MYC even within one cell division cycle resulted in a several-magnitude increase in the frequency of chromosomal breaks and translocations in normal human cells. Hence, MYC overexpression may be a previously undescribed example of a dominant mutator that may fuel tumorigenesis by inducing chromosomal damage.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Witasp, Erika; Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Gustafsson, Ann-Catrin
2005-05-13
Previous studies have suggested that 1,25(OH){sub 2}D{sub 3}, the active form of vitamin D{sub 3}, may increase the survival of bone-forming osteoblasts through an inhibition of apoptosis. On the other hand, vitamin D{sub 3} has also been shown to trigger apoptosis in human cancer cells, including osteosarcoma-derived cell lines. In the present study, we show that 1,25(OH){sub 2}D{sub 3} induces a time- and dose-dependent loss of cell viability in the rat osteosarcoma cell line, UMR-106, and the human osteosarcoma cell line, TE-85. We were unable, however, to detect nuclear condensation, phosphatidylserine externalization, or other typical signs of apoptosis in thismore » model. Moreover, 1,25(OH){sub 2}D{sub 3} failed to protect against apoptosis induced by serum starvation or incubation with the protein kinase inhibitor, staurosporine. These in vitro findings are thus at variance with several previous reports in the literature and suggest that induction of or protection against apoptosis of bone-derived cells may not be a primary function of vitamin D{sub 3}.« less
Online health communication about human genetics: perceptions and preferences of internet users.
Bernhardt, Jay M; McClain, Jacqueline; Parrott, Roxanne L
2004-12-01
Unprecedented advancements in human genetics research necessitate keeping the public abreast of new information, applications, and implications and the Internet represents an important method of communicating with the public. Our research used cross-sectional self-report survey data collected from a diverse convenience sample of 780 Internet users in two states. Multivariate regression analysis explored the relationships between experiences, perceptions, and preferences for online health and genetics communication. Online health information seeking was associated with previous genetic information seeking, comfort with online genetic communication, perceived risk for genetic abnormality, being female, and having more education. Comfort with online genetics communication was associated with a preference for online genetic information, previous online health and off-line genetics information seeking, having a healthy lifestyle, believing in the positive impact of human genetics research, and being female. Perceiving online health information to be accurate was associated with preferring the Internet for genetics communication, being older, less educated, and perceiving Internet use as anonymous. Preferring online genetics communication to other communication channels was associated with perceiving online health information as accurate, being comfortable receiving online genetics information, having lower intrinsic religiosity, and being male. The implications of findings for Web-based health message design are discussed.
Płoneczka-Janeczko, Katarzyna; Rypuła, Krzysztof
2016-01-01
Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a significant pathogen in both human medicine and veterinary medicine. The importance of pets as reservoirs of human infections is still poorly understood. This article provides detailed information of a cross-sectional study of a S. aureus colonization in clinically healthy indoor cats. The study systematically assessed a number of different anatomical locations for the S. aureus colonization and the influence of a range of potential risk factors on the value of the final S. aureus colonization rate. The incidence rates observed for cats with at least one site positive for S. aureus or MRSA were 17.5% and 6.63%, respectively. The following risk factors were identified: one or more owners working in the healthcare industry (human or veterinary); dogs being kept with the cat under investigation; treatment of the cat under investigation with antibiotics or chemotherapeutics during the previous year. In conclusion, this study revealed a higher prevalence of MRSA than what has previously been reported in healthy pets. A combination of anatomical locations from which the samples were collected had a major influence on the final value of the S. aureus colonization rate. PMID:27766257
Methamphetamine-related brainstem haemorrhage.
Chiu, Zelia K; Bennett, Iwan E; Chan, Patrick; Rosenfeld, Jeffrey V
2016-10-01
We report the case of an otherwise healthy 29-year-old woman who presented with a brainstem haemorrhage following intravenous methamphetamine use. Extensive investigation did not reveal an underlying pathology, and the development of symptoms was temporally related to methamphetamine injection. Although intracerebral haemorrhage secondary to methamphetamine use is well documented, this report describes a haemorrhage within the brainstem which is a rare location. While animal studies have demonstrated the potential of methamphetamines to produce brainstem haemorrhages, there has only been one previous report describing a haemorrhage in this location due to amphetamine use in humans. We conclude with a brief discussion of the clinical features and aetiology of methamphetamine-related stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.
Carballeira, Néstor M.; Sanabria, David; Oyola, Delise
2006-01-01
An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid was developed based on the appropriate use of (trimethylsilyl)acetylene as the key reagent in the synthesis. The reported synthesis started with commercially available 8-bromo-1-octanol and furnished the desired acid in seven steps and in a 16% overall yield, a significant improvement over the previous reported synthesis for this fatty acid. The synthesis reported herein afforded sufficient amounts to study the acid topoisomerase I inhibitory potential and it was found that the title acid inhibits the human placenta DNA topoisomerase I enzyme at concentrations of 500 μM. PMID:17680032
Recombinant adeno-associated virus targets passenger gene expression to cones in primate retina
NASA Astrophysics Data System (ADS)
Mancuso, Katherine; Hendrickson, Anita E.; Connor, Thomas B., Jr.; Mauck, Matthew C.; Kinsella, James J.; Hauswirth, William W.; Neitz, Jay; Neitz, Maureen
2007-05-01
Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy of photoreceptor-based diseases. Previous studies have demonstrated that rAAV serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and dogs, and it can target rods, but not cones in primates. Here we report that using a human cone-specific enhancer and promoter to regulate expression of a green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully targeted expression of the reporter gene to primate cones, and the time course of GFP expression was able to be monitored in a living animal using the RetCam II digital imaging system.
Development of Preference for Conspecific Faces in Human Infants
ERIC Educational Resources Information Center
Sanefuji, Wakako; Wada, Kazuko; Yamamoto, Tomoka; Mohri, Ikuko; Taniike, Masako
2014-01-01
Previous studies have proposed that humans may be born with mechanisms that attend to conspecifics. However, as previous studies have relied on stimuli featuring human adults, it remains unclear whether infants attend only to adult humans or to the entire human species. We found that 1-month-old infants (n = 23) were able to differentiate between…
De novo assembly of a haplotype-resolved human genome.
Cao, Hongzhi; Wu, Honglong; Luo, Ruibang; Huang, Shujia; Sun, Yuhui; Tong, Xin; Xie, Yinlong; Liu, Binghang; Yang, Hailong; Zheng, Hancheng; Li, Jian; Li, Bo; Wang, Yu; Yang, Fang; Sun, Peng; Liu, Siyang; Gao, Peng; Huang, Haodong; Sun, Jing; Chen, Dan; He, Guangzhu; Huang, Weihua; Huang, Zheng; Li, Yue; Tellier, Laurent C A M; Liu, Xiao; Feng, Qiang; Xu, Xun; Zhang, Xiuqing; Bolund, Lars; Krogh, Anders; Kristiansen, Karsten; Drmanac, Radoje; Drmanac, Snezana; Nielsen, Rasmus; Li, Songgang; Wang, Jian; Yang, Huanming; Li, Yingrui; Wong, Gane Ka-Shu; Wang, Jun
2015-06-01
The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.
Late quaternary regional geoarchaeology of Southeast Alaska Karst: A progress report
Dixon, E.J.; Heaton, T.H.; Fifield, T.E.; Hamilton, T.D.; Putnam, D.E.; Grady, F.
1997-01-01
Karst systems, sea caves, and rock shelters within the coastal temperate rain forest of Alaska's Alexander Archipelago preserve important records of regional archaeology, sea level history, glacial and climatic history, and vertebrate paleontology. Two 14C AMS dates on human bone discovered in a remote cave (49-PET-408) on Prince of Wales Island document the oldest reliably dated human in Alaska to ca. 9800 B.P. A series of 14C AMS dates from cave deposits span the past 40,000 years and provide the first evidence of Pleistocene faunas from the northwest coast of North America. Other discoveries include sea caves and marine beach deposits elevated above modern sea level, extensive solution caves, and mammalian remains of species previously undocumented within the region. Records of human activity, including cave art, artifacts, and habitation sites may provide new insights into the early human colonization of the Americas. ??1997 John Wiley & Sons, Inc.
Gracia, Ana; Arsuaga, Juan Luis; Martínez, Ignacio; Lorenzo, Carlos; Carretero, José Miguel; Bermúdez de Castro, José María; Carbonell, Eudald
2009-04-21
We report here a previously undescribed human Middle Pleistocene immature specimen, Cranium 14, recovered at the Sima de los Huesos (SH) site (Atapuerca, Spain), that constitutes the oldest evidence in human evolution of a very rare pathology in our own species, lambdoid single suture craniosynostosis (SSC). Both the ecto- and endo-cranial deformities observed in this specimen are severe. All of the evidence points out that this severity implies that the SSC occurred before birth, and that facial asymmetries, as well as motor/cognitive disorders, were likely to be associated with this condition. The analysis of the present etiological data of this specimen lead us to consider that Cranium 14 is a case of isolated SSC, probably of traumatic origin. The existence of this pathological individual among the SH sample represents also a fact to take into account when referring to sociobiological behavior in Middle Pleistocene humans.
Cloning, structure, and chromosome localization of the mouse glutaryl-CoA dehydrogenase gene
DOE Office of Scientific and Technical Information (OSTI.GOV)
Koeller, D.M.; DiGiulio, A.; Frerman, F.E.
Glutaryl-CoA dehydrogenase (GCDH) is a nuclear-encoded, mitochondrial matrix enzyme. In humans, deficiency of GCDH leads to glutaric acidemia type I, and inherited disorder of amino acid metabolism characterized by a progressive neurodegenerative disease. In this report we describe the cloning and structure of the mouse GCDH (Gcdh) gene and cDNA and its chromosomal localization. The mouse Gcdh cDNA is 1.75 kb long and contains and open reading frame of 438 amino acids. The amino acid sequences of mouse, human, and pig GCDH are highly conserved. The mouse Gcdh gene contains 11 exons and spans 7 kb of genomic DNA. Gcdhmore » was mapped by backcross analysis to mouse chromosome 8 within a region that is homologous to a region of human chromosome 19, where the human gene was previously mapped. 14 refs., 3 figs.« less
Polymerized soluble venom--human serum albumin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patterson, R.; Suszko, I.M.; Grammer, L.C.
Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. /sup 125/I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera againstmore » bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.« less
Oxidative stress and NO generation in the rat pancreatitis induced by pancreatic duct ligation.
Buchwalow, Igor; Schnekenburger, Jürgen; Atiakshin, Dmitri; Samoilova, Vera; Wolf, Eduard; Boecker, Werner; Tiemann, Katharina
2017-04-01
The interaction between nitric oxide (NO) and superoxides is critical in the development of an acute pancreatitis. Previously, we reported that the expression of superoxides and of the NO-generating enzyme (NO synthase, NOS) was up-regulated in the human pancreatitis, especially within the exocrine compartment indicating an exceptional susceptibility of the exocrine parenchyma to oxidative stress. The aim of the present study was to compare the regulation of NO signalling pathways in the human pancreatitis and in an animal model of an acute pancreatitis induced by pancreatic duct ligation (PDL) in rats. In the PDL-induced rat pancreatitis, we revealed a similar pattern of oxidative stress and NOS up-regulation in acinar and in ductal compartments, like in the human pancreatitis. This demonstrates that the PDL-induced rat pancreatitis is a proper model for further studies of acute pancreatitis development in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.
Establishment of an evaluation model for human milk fat substitutes.
Wang, Yong-Hua; Mai, Qing-Yun; Qin, Xiao-Li; Yang, Bo; Wang, Zi-Lian; Chen, Hai-Tian
2010-01-13
Fatty acid composition and distribution of human milk fat (HMF), from mothers over different lactating periods in Guangzhou, China, were analyzed. The universal characteristics were consistent with previously reported results although the fatty acid content was within a different range and dependent on the local population (low saturated fatty acid and high oleic acid for Guangdong mothers' milk fat). Based on the composition of the total and sn-2 fatty acids of mature milk fat, an efficient evaluation model was innovatively established by adopting the "deducting score" principle. The model showed good agreement between the scores and the degree of similarity by assessing 15 samples from different sources including four samples of HMF, eight samples of human milk fat substitutes (HMFSs) and infant formulas, and three samples of fats and oils. This study would allow for the devolvement of individual human milk fat substitutes with different and specific fatty acid compositions for local infants.
Gracia, Ana; Arsuaga, Juan Luis; Martínez, Ignacio; Lorenzo, Carlos; Carretero, José Miguel; Bermúdez de Castro, José María; Carbonell, Eudald
2009-01-01
We report here a previously undescribed human Middle Pleistocene immature specimen, Cranium 14, recovered at the Sima de los Huesos (SH) site (Atapuerca, Spain), that constitutes the oldest evidence in human evolution of a very rare pathology in our own species, lambdoid single suture craniosynostosis (SSC). Both the ecto- and endo-cranial deformities observed in this specimen are severe. All of the evidence points out that this severity implies that the SSC occurred before birth, and that facial asymmetries, as well as motor/cognitive disorders, were likely to be associated with this condition. The analysis of the present etiological data of this specimen lead us to consider that Cranium 14 is a case of isolated SSC, probably of traumatic origin. The existence of this pathological individual among the SH sample represents also a fact to take into account when referring to sociobiological behavior in Middle Pleistocene humans. PMID:19332773
Effects of scopolamine and dextroamphetamine on human performance
NASA Technical Reports Server (NTRS)
Schmedtje, John F., Jr.; Oman, Charles M.; Letz, Richard; Baker, Edward L.
1988-01-01
The effects of two drugs used to prevent symptoms of motion sickness in the operational environment were examined in this study of human performance as measured by computer-based tests of cognitive and psychomotor skills. Each subject was exposed repetitively to five tests: symbol-digit substitution, simple reaction time, pattern recognition, digit span memory, and pattern memory. Although there have been previous reports of decreases in human performance in similar testing with higher dosages of scopolamine or dextroamphetamine, no significant decrements were observed with the operational-level combined dose used in this study (0.4 mg oral scopolamine and 5.0 mg oral dextroamphetamine.) The controversy over the use of combination drug therapy in this environnment is discussed along with the indications for further research based on the findings.
Pairing of heterochromatin in response to cellular stress.
Abdel-Halim, H I; Mullenders, L H F; Boei, J J W A
2006-07-01
We previously reported that exposure of human cells to DNA-damaging agents (X-rays and mitomycin C (MMC)) induces pairing of the homologous paracentromeric heterochromatin of chromosome 9 (9q12-13). Here, we show that UV irradiation and also heat shock treatment of human cells lead to similar effects. Since the various agents induce very different types and frequencies of damage to cellular constituents, the data suggest a general stress response as the underlying mechanism. Moreover, local UV irradiation experiments revealed that pairing of heterochromatin is an event that can be triggered without induction of DNA damage in the heterochromatic sequences. The repair deficient xeroderma pigmentosum cells (group F) previously shown to fail pairing after MMC displayed elevated pairing after heat shock treatment but not after UV exposure. Taken together, the present results indicate that pairing of heterochromatin following exposure to DNA-damaging agents is initiated by a general stress response and that the sensing of stress or the maintenance of the paired status of the heterochromatin might be dependent on DNA repair.
NASA Astrophysics Data System (ADS)
Baek, Inseok
The purpose of this research is to describe the development of a mathematical model of diffusion, convection, and lateral transport into the airway wall and alveolar absorption for inhaled radioactive gases in the human conductive and respiratory airways based on a Single Path Trumpet-bell model (SPM). Mathematical simulation models have been used successfully to study transport, absorption into the blood through alveoli, and lung tissue uptake of soluble and nonreactive radioactive gases. Results from such simulations also show clearly that inhaled radioactive gases are absorbed into the lung tissues as well as into the blood through the alveoli. In contrast to previous reports in the literature, the present study found that blood uptake through alveoli is much greater than that calculated previously. Regional depositions in the lung from inhaled radioactive gases are presented as the result of this simulation. The committed effective dose to lung tissue due to submersion in radioactive clouds has been newly defined using the results of this simulation.
The impact of strain-specific immunity on Lyme disease incidence is spatially heterogeneous.
Khatchikian, Camilo E; Nadelman, Robert B; Nowakowski, John; Schwartz, Ira; Wormser, Gary P; Brisson, Dustin
2017-12-01
Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne infection in the US. Recent studies have demonstrated that the incidence of human Lyme disease would have been even greater were it not for the presence of strain-specific immunity, which protects previously infected patients against subsequent infections by the same B. burgdorferi strain. Here, spatial heterogeneity is incorporated into epidemiological models to accurately estimate the impact of strain-specific immunity on human Lyme disease incidence. The estimated reduction in the number of Lyme disease cases is greater in epidemiologic models that explicitly include the spatial distribution of Lyme disease cases reported at the county level than those that utilize nationwide data. strain-specific immunity has the greatest epidemiologic impact in geographic areas with the highest Lyme disease incidence due to the greater proportion of people that have been previously infected and have developed strain-specific immunity. Copyright © 2017 Elsevier Inc. All rights reserved.
SIRT2 and lysine fatty acylation regulate the transforming activity of K-Ras4a
Wisner, Stephanie A; Chen, Xiao; Spiegelman, Nicole A; Linder, Maurine E
2017-01-01
Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a. We further demonstrate that SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a, enhances its interaction with A-Raf, and thus promotes cellular transformation. Our study identifies lysine fatty acylation as a previously unknown regulatory mechanism for the Ras family of GTPases that is distinct from cysteine fatty acylation. These findings highlight the biological significance of lysine fatty acylation and sirtuin-catalyzed protein lysine defatty-acylation. PMID:29239724
Cottom, Hannah; Rengabashyam, Bhavani; Turton, Philip E; Shaaban, Abeer M
2014-05-23
Inclusions of ectopic breast tissue in axillary lymph nodes are reported very infrequently and typically are only identified microscopically as an incidental finding. Furthermore the development of a benign proliferative lesion in the form of an intraductal papilloma from intranodal ectopic breast tissue is an extremely rare phenomenon with only three previous cases reported. This report describes an unusual and rare case of an intraductal papilloma arising in an axillary lymph node of a patient known to have the human immunodeficiency virus. A 40-year-old Black African woman underwent excision of an enlarged palpable axillary lymph node. In the preceding 7 years she had received at least six separate surgical excisions to her ipsilateral breast for papillomatosis. The last surgical intervention was performed 1 year prior to presentation with an enlarged axillary lymph node. Histological examination of her axillary lymph node revealed a papillomatous proliferative epithelial lesion within an apparent encompassing duct, resembling a mammary intraductal papilloma. In the surrounding lymphoid tissue small groups of duct-like structures were additionally noted. Immunostaining with a panel of myoepithelial markers in conjunction with oestrogen receptor produced a mixed heterogeneous staining pattern in both the papillomatous lesion and the peripheral duct-like structures. This confirmed the diagnosis of a benign intraductal papilloma within an axillary lymph node, considered to have arisen from ectopic breast tissue. This case demonstrates that intranodal ectopic breast tissue has the potential to undergo benign proliferative change albeit extremely rarely. Therefore this possibility must be considered to ensure the correct diagnosis is made. In addition, to the best of our knowledge, this is the first case report which has described recurrent intraductal papillomas and the subsequent development of an intraductal papilloma within an ipsilateral axillary lymph node, in a patient who is human immunodeficiency virus positive. There is minimal literature investigating the specific types of breast pathologies experienced by patients infected with human immunodeficiency virus and it remains unexplored as to whether human immunodeficiency virus may lead to proliferative papillomatous epithelial changes. This report considers the role of the human papillomavirus and recommends that further investigatory studies are required.
Gonadal and Sex Differentiation Abnormalities of Dogs and Cats
Meyers-Wallen, V.N.
2012-01-01
The molecular steps in normal sexual development were largely discovered by studying patients and animal models with disorders of sexual development (DSD). Although several types of DSD have been reported in the cat and dog, which are often strikingly similar to human DSD, these have been infrequently utilized to contribute to our knowledge of mammalian sexual development. Canine and feline cases of DSD with sufficient evidence to be considered as potential models are summarized in this report. The consensus DSD terminology, and reference to previous terminology, is used to foster adoption of a common nomenclature that will facilitate communication and collaboration between veterinarians, physicians, and researchers. To efficiently utilize these unique resources as molecular tools continue to improve, it will be helpful to deposit samples from valuable cases into repositories where they are available to contribute to our understanding of sexual development, and thus improve human and animal health. PMID:22005097
Confirmation of RAX gene involvement in human anophthalmia
Lequeux, L.; Rio, Marlène; Vigouroux, Armelle; Titeux, Matthias; Etchevers, Heather; Malecaze, François; Chassaing, Nicolas; Calvas, Patrick
2008-01-01
Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. Mutations in several genes have been involved in syndromic and non-syndromic anophthalmia. Previously, RAX recessive mutations were implicated in a single patient with right anophthalmia and left microphthalmia and sclerocornea. Here, we report the findings of novel compound heterozygous RAX mutations in a child with bilateral anophthalmia. Both mutations are located in exon 3. c.664delT is a frameshifting deletion predicted to introduce a premature stop codon (p.Ser222ArgfsX62), and c.909 C>G is a nonsense mutation with similar consequences (p.Tyr303X). This is the second report of a patient with anophthalmia caused by RAX mutations. These findings confirm that RAX plays a major role in the early stages of eye development and is involved in human anophthalmia. PMID:18783408
Confirmation of RAX gene involvement in human anophthalmia.
Lequeux, L; Rio, M; Vigouroux, A; Titeux, M; Etchevers, H; Malecaze, F; Chassaing, N; Calvas, P
2008-10-01
Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. Mutations in several genes have been involved in syndromic and non-syndromic anophthalmia. Previously, RAX recessive mutations were implicated in a single patient with right anophthalmia, left microphthalmia and sclerocornea. In this study, we report the findings of novel compound heterozygous RAX mutations in a child with bilateral anophthalmia. Both mutations are located in exon 3. c.664delT is a frameshifting deletion predicted to introduce a premature stop codon (p.Ser222ArgfsX62), and c.909C>G is a nonsense mutation with similar consequences (p.Tyr303X). This is the second report of a patient with anophthalmia caused by RAX mutations. These findings confirm that RAX plays a major role in the early stages of eye development and is involved in human anophthalmia.
Artificial intelligence systems based on texture descriptors for vaccine development.
Nanni, Loris; Brahnam, Sheryl; Lumini, Alessandra
2011-02-01
The aim of this work is to analyze and compare several feature extraction methods for peptide classification that are based on the calculation of texture descriptors starting from a matrix representation of the peptide. This texture-based representation of the peptide is then used to train a support vector machine classifier. In our experiments, the best results are obtained using local binary patterns variants and the discrete cosine transform with selected coefficients. These results are better than those previously reported that employed texture descriptors for peptide representation. In addition, we perform experiments that combine standard approaches based on amino acid sequence. The experimental section reports several tests performed on a vaccine dataset for the prediction of peptides that bind human leukocyte antigens and on a human immunodeficiency virus (HIV-1). Experimental results confirm the usefulness of our novel descriptors. The matlab implementation of our approaches is available at http://bias.csr.unibo.it/nanni/TexturePeptide.zip.
Crystal structures of inhibitor complexes of human T-cell leukemia virus (HTLV-1) protease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Satoh, Tadashi; Li, Mi; Nguyen, Jeffrey-Tri
2010-09-28
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailedmore » study of structure-activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease.« less
Crystal Structures of Inhibitir Complexes of Human T-Cell Leukemia Virus (HTLV-1) Protease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Satoh, Tadashi; Li, Mi; Nguyen, Jeffrey-Tri
2010-09-17
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailedmore » study of structure-activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease.« less
Prediction error induced motor contagions in human behaviors.
Ikegami, Tsuyoshi; Ganesh, Gowrishankar; Takeuchi, Tatsuya; Nakamoto, Hiroki
2018-05-29
Motor contagions refer to implicit effects on one's actions induced by observed actions. Motor contagions are believed to be induced simply by action observation and cause an observer's action to become similar to the action observed. In contrast, here we report a new motor contagion that is induced only when the observation is accompanied by prediction errors - differences between actions one observes and those he/she predicts or expects. In two experiments, one on whole-body baseball pitching and another on simple arm reaching, we show that the observation of the same action induces distinct motor contagions, depending on whether prediction errors are present or not. In the absence of prediction errors, as in previous reports, participants' actions changed to become similar to the observed action, while in the presence of prediction errors, their actions changed to diverge away from it, suggesting distinct effects of action observation and action prediction on human actions. © 2018, Ikegami et al.
Facial asymmetry as an indicator of psychological, emotional, and physiological distress.
Shackelford, T K; Larsen, R J
1997-02-01
Fluctuating asymmetry (FA) is deviation from bilateral symmetry in morphological traits with asymmetry values that are normally distributed with a mean of 0. FA is produced by genetic or environmental perturbations of developmental design and may play a role in human sexual selection. K. Grammer and R. Thornhill (1994) found that facial FA negatively covaries with observer ratings of attractiveness, dominance, sexiness, and health. Using self-reports, observer ratings, daily diary reports, and psychophysiological measures, the authors assessed the relationship between facial FA and health in 2 samples of undergraduates (N = 101). Results partially replicate and extend those of K. Grammer and R. Thornhill (1994) and suggest that facial FA may signal psychological, emotional, and physiological distress. Discussion integrates the authors' findings with previous research on FA and suggests future research needed to clarify the role of FA in human sexual selection.
Increased choline kinase activity in 1,2-dimethylhydrazine-induced rat colon cancer.
Nakagami, K; Uchida, T; Ohwada, S; Koibuchi, Y; Morishita, Y
1999-11-01
Cancer cells acquire particular characteristics that benefit their proliferation. We previously reported that human colon cancers examined had increased choline kinase activity and phosphocholine levels. The elevated phosphocholine levels were in part due to both activation of choline kinase and increased choline kinase alpha protein levels. In this report, we analyzed choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in rat 1,2-dimethylhydrazine (DMH)-induced colon cancer. This study is the first to demonstrate increased choline kinase alpha enzymatic activity, protein levels, and mRNA levels in DMH-induced colon cancer as well as human colon cancer, although phosphocholine was not increased in DMH-induced rat cancer. The increase in the mRNA level was partly due to an increase in the transcription of the choline kinase alpha gene. The increased choline kinase activity may be a specific characteristic acquired by cancer cells that benefits their proliferation.
Chen, Bo; Li, Wen-Ta; Wang, Fun-In
2018-05-01
Nephroblastomas are uncommon embryonal tumors in dogs. We report herein a blastema-predominant nephroblastoma with gingival metastasis in an 8-y-old Miniature Pinscher dog. Histologically, the mass was composed mainly of blastemal elements with minor epithelial and mesenchymal differentiation. Metastatic masses in the gingiva had histologic and immunohistochemical features similar to those of the primary renal nephroblastoma. Neoplastic cells were extensively positive for both vimentin and PAX8, and scattered positive for cytokeratin. Using the clinical staging of human Wilms tumor, we staged our case as stage IV with <4 mo of survival time. We summarized previous studies of canine renal and spinal nephroblastomas, and analyzed the correlations among clinical staging, histologic classification, and mean survival time of dogs with renal nephroblastomas. Clinical staging was significantly correlated with survival time, as shown in humans. In dogs, however, additional factors can potentially influence the outcome of treatment and disease development.
Genomic copy number variations in three Southeast Asian populations.
Ku, Chee-Seng; Pawitan, Yudi; Sim, Xueling; Ong, Rick T H; Seielstad, Mark; Lee, Edmund J D; Teo, Yik-Ying; Chia, Kee-Seng; Salim, Agus
2010-07-01
Research on the role of copy number variations (CNVs) in the genetic risk of diseases in Asian populations has been hampered by a relative lack of reference CNV maps for Asian populations outside the East Asians. In this article, we report the population characteristics of CNVs in Chinese, Malay, and Asian Indian populations in Singapore. Using the Illumina Human 1M Beadchip array, we identify 1,174 CNV loci in these populations that corroborated with findings when the same samples were typed on the Affymetrix 6.0 platform. We identify 441 novel loci not previously reported in the Database of Genomic Variations (DGV). We observe a considerable number of loci that span all three populations and were previously unreported, as well as population-specific loci that are quite common in the respective populations. From this we observe the distribution of CNVs in the Asian Indian population to be considerably different from the Chinese and Malay populations. About half of the deletion loci and three-quarters of duplication loci overlap UCSC genes. Tens of loci show population differentiation and overlap with genes previously known to be associated with genetic risk of diseases. One of these loci is the CYP2A6 deletion, previously linked to reduced susceptibility to lung cancer. (c) 2010 Wiley-Liss, Inc.
Bobadilla-del Valle, Miriam; Torres-González, Pedro; Cervera-Hernández, Miguel Enrique; Martínez-Gamboa, Areli; Crabtree-Ramirez, Brenda; Chávez-Mazari, Bárbara; Ortiz-Conchi, Narciso; Rodríguez-Cruz, Luis; Cervantes-Sánchez, Axel; Gudiño-Enríquez, Tomasa; Cinta-Severo, Carmen; Sifuentes-Osornio, José; Ponce de León, Alfredo
2015-09-01
Mycobacterium tuberculosis causes the majority of tuberculosis (TB) cases in humans; however, in developing countries, human TB caused by M. bovis may be frequent but undetected. Human TB caused by M. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, and it is less frequently attributed to animal-to-human or human-to-human contact. We describe the trends of M. bovis isolation from human samples and first-line drug susceptibility during a 15-year period in a referral laboratory located in a tertiary care hospital in Mexico City. Data on mycobacterial isolates from human clinical samples were retrieved from the laboratory's database for the 2000-2014 period. Susceptibility to first-line drugs: rifampin, isoniazid, streptomycin (STR) and ethambutol was determined. We identified 1,165 isolates, 73.7% were M. tuberculosis and 26.2%, M. bovis. Among pulmonary samples, 16.6% were M. bovis. The proportion of M. bovis isolates significantly increased from 7.8% in 2000 to 28.4% in 2014 (X(2)trend, p<0.001). Primary STR resistance was higher among M. bovis compared with M. tuberculosis isolates (10.9% vs.3.4%, p<0.001). Secondary multidrug resistance (MDR) rates were 38.5% and 34.4% for M. bovis and M. tuberculosis, respectively (p = 0.637). A rising trend of primary STR monoresistance was observed for both species (3.4% in 2000-2004 vs. 7.6% in 2010-2014; p = 0.02). There is a high prevalence and a rising trend of M. bovis isolates in our region. The proportion of pulmonary M. bovis isolates is higher than in previous reports. Additionally, we report high rates of primary anti-tuberculosis resistance and secondary MDR in both M. tuberculosis and M. bovis. This is one of the largest reports on drug susceptibility of M. bovis from human samples and shows a significant proportion of first-line anti-tuberculosis drug resistance.
Kessler, C; Oldenburg, J; Ettingshausen, C Escuriola; Tiede, A; Khair, K; Négrier, C; Klamroth, R
2015-01-01
Inhibitor development is the most serious and challenging complication in the treatment of severe haemophilia A. Up to 38% of such patients develop inhibitors with current recombinant factor VIII (rFVIII) products produced in hamster cell lines. Human-cl rhFVIII is a new generation fully sulfated B-domain-deleted FVIII coagulant glycoprotein, which is generated from a human cell line. Thus, there are no non-human epitopes which would be potentially immunogenic. This molecule has significantly higher VWF-binding affinity compared with existing full-length rFVIII produced in hamster cell lines. The development aim of Human-cl rhFVIII is to address the challenges of FVIII inhibitors and frequent infusions during prophylaxis. Human-cl rhFVIII's mean half-life is very comparable to some of the newer products which involve modification of the FVIII molecule to extend the circulating half-life. There are promising data concerning the use of a personalized prophylaxis regimen with Human-cl rhFVIII. Preliminary data indicate a median dosing interval of 3.5 days with 66.7% of the patients on a twice per week or fewer infusions schedule combined with a low bleeding rate and no increased FVIII consumption when compared to standard prophylaxis. No product-specific laboratory assay is required to monitor the coagulation activity for Human-cl rhFVIII. The results of registration clinical trials with Human-cl rhFVIII as well as the ongoing studies in previously untreated patients (NuProtect) and personalized prophylaxis study in previously treated patients (NuPreviq), will be discussed. The manufacturer has received marketing authorization for Human-cl rhFVIII in Europe and Canada under the name Nuwiq(®) and plans to launch it in the USA and globally in 2015. © 2014 John Wiley & Sons Ltd.
Caldas, Cristina; Coelho, Verônica; Kalil, Jorge; Moro, Ana Maria; Maranhão, Andrea Q; Brígido, Marcelo M
2003-05-01
Humanization of monoclonal antibodies by complementary determinant region (CDR)-grafting has become a standard procedure to improve the clinical usage of animal antibodies. However, antibody humanization may result in loss of activity that has been attributed to structural constraints in the framework structure. In this paper, we report the complete humanization of the 6.7 anti-human CD18 monoclonal antibody in a scFv form. We used a germline-based approach to design a humanized VL gene fragment and expressed it together with a previously described humanized VH. The designed humanized VL has only 14 mutations compared to the closest human germline sequence. The resulting humanized scFv maintained the binding capacity and specificity to human CD18 expressed on the cell surface of peripheral blood mononuclear cells (PBMC), and showed the same pattern of staining T-lymphocytes sub-populations, in comparison to the original monoclonal antibody. We observed an unexpected effect of a conserved mouse-human framework position (L37) that hinders the binding of the humanized scFv to antigen. This paper reveals a new framework residue that interferes with paratope and antigen binding and also reinforces the germline approach as a successful strategy to humanize antibodies.
Diede, Scott J; Yao, Zizhen; Keyes, C Chip; Tyler, Ashlee E; Dey, Joyoti; Hackett, Christopher S; Elsaesser, Katrina; Kemp, Christopher J; Neiman, Paul E; Weiss, William A; Olson, James M; Tapscott, Stephen J
2013-12-01
Genetic and epigenetic alterations are essential for the initiation and progression of human cancer. We previously reported that primary human medulloblastomas showed extensive cancer-specific CpG island DNA hypermethylation in critical developmental pathways. To determine whether genetically engineered mouse models (GEMMs) of medulloblastoma have comparable epigenetic changes, we assessed genome-wide DNA methylation in three mouse models of medulloblastoma. In contrast to human samples, very few loci with cancer-specific DNA hypermethylation were detected, and in almost all cases the degree of methylation was relatively modest compared with the dense hypermethylation in the human cancers. To determine if this finding was common to other GEMMs, we examined a Burkitt lymphoma and breast cancer model and did not detect promoter CpG island DNA hypermethylation, suggesting that human cancers and at least some GEMMs are fundamentally different with respect to this epigenetic modification. These findings provide an opportunity to both better understand the mechanism of aberrant DNA methylation in human cancer and construct better GEMMs to serve as preclinical platforms for therapy development.
Expression of the diabetes risk gene wolframin (WFS1) in the human retina
Schmidt-Kastner, Rainald; Kreczmanski, Pawel; Preising, Markus; Diederen, Roselie; Schmitz, Christoph; Reis, Danielle; Blanks, Janet; Dorey, C. Kathleen
2009-01-01
Wolfram syndrome 1 (WFS1, OMIM 222300), a rare genetic disorder characterized by optic nerve atrophy, deafness, diabetes insipidus and diabetes mellitus, is caused by mutations of WFS1, encoding WFS1/wolframin. Non-syndromic WFS1 variants are associated with the risk of diabetes mellitus due to altered function of wolframin in pancreatic islet cells, expanding the importance of wolframin. This study extends a previous report for the monkey retina, using immunohistochemistry to localize wolframin on cryostat and paraffin sections of human retina. In addition, the human retinal pigment epithelial (RPE) cell line termed ARPE-19 and retinas from both pigmented and albino mice were studied to assess wolframin localization. In the human retina, wolframin was expressed in retinal ganglion cells, optic axons and the proximal optic nerve. Wolframin expression in the human retinal pigment epithelium (RPE) was confirmed with intense cytoplasmic labeling in ARPE-19 cells. Strong labeling of the RPE was also found in the albino mouse retina. Cryostat sections of the mouse retina showed a more extended pattern of wolframin labeling, including the inner nuclear layer (INL) and photoreceptor inner segments, confirming the recent report of Kawano et al. (J. Comp. Neurol. 2008: 510, 1-23). Absence of these cells in the human specimens despite the use of human-specific antibodies to wolframin may be related to delayed fixation. Loss of wolframin function in RGCs and the unmyelinated portion of retinal axons could explain optic nerve atrophy in Wolfram Syndrome 1. PMID:19523951
Manning, Lois R.; Russell, J. Eric; Popowicz, Anthony M.; Manning, Robert S.; Padovan, Julio C.; Manning, James M.
2013-01-01
A previously unrecognized function of normal human hemoglobins occurring during protein assembly is described - - self-regulation of subunit pairings and their durations arising from the variable strengths of their subunit interactions. Although it is known that many mutant human hemoglobins have altered subunit interface strengths, those of the normal embryonic, fetal, and adult human hemoglobins have not been considered to differ significantly. However, in a comprehensive study of both types of subunit interfaces of seven of the eight normal oxy human hemoglobins, we found that the strength, i.e. the free energies of the tetramer-dimer interfaces, contrary to previous reports, differ by 3-orders of magnitude and display an undulating profile similar to the transitions (“switches”) of various globin subunit types over time. The dimer interface strengths are also variable and correlate linearly with their developmental profile; embryonic hemoglobins are the weakest, fetal hemoglobin is of intermediate strength, and adult hemoglobins are the strongest. The pattern also correlates generally with their different O2 affinities and responses to allosteric regulatory molecules. Acetylation of fetal hemoglobin weakens its unusually strong subunit interactions and occurs progressively as its expression diminishes and adult hemoglobin A formations begins; a causal relationship is suggested. The relative contributions of globin gene order and competition among subunits due to differences in their interface strengths were found to be complementary and establish a connection between genetics, thermodynamics, and development. PMID:19583196
Ciszewski, Marcin; Zegarski, Kamil; Szewczyk, Eligia M
2016-11-01
Streptococcus dysgalactiae is a pyogenic species pathogenic both for humans and animals. Until recently, it has been considered an exclusive animal pathogen causing infections in wild as well as domestic animals. Currently, human infections are being reported with increasing frequency, and their clinical picture is often similar to the ones caused by Streptococcus pyogenes. Due to the fact that S. dysgalactiae is a heterogeneous species, it was divided into two subspecies: S. dysgalactiae subsp. equisimilis (SDSE) and S. dysgalactiae subsp. dysgalactiae (SDSD). The first differentiation criterion, described in 1996, was based on strain isolation source. Currently applied criteria, published in 1998, are based on hemolysis type and Lancefield group classification. In this study, we compared subspecies identification results for 36 strains isolated from clinical cases both in humans and animals. Species differentiation was based on two previously described criteria as well as MALDI-TOF and genetic analyses: RISA and 16S rRNA genes sequencing. Antimicrobial susceptibility profiles were also determined according to CLSI guidelines. The results presented in our study suggest that the subspecies differentiation criteria previously described in the above two literature positions seem to be inaccurate in analyzed group of strains, the hemolysis type on blood agar, and Lancefield classification should not be here longer considered as criteria in subspecies identification. The antimicrobial susceptibility tests indicate emerging of multiresistant human SDSE strains resistant also to vancomycin, linezolid and tigecycline, which might pose a substantial problem in treatment.
Trombetta, Beniamino; Sellitto, Daniele; Scozzari, Rosaria; Cruciani, Fulvio
2014-01-01
It has long been believed that the male-specific region of the human Y chromosome (MSY) is genetically independent from the X chromosome. This idea has been recently dismissed due to the discovery that X–Y gametologous gene conversion may occur. However, the pervasiveness of this molecular process in the evolution of sex chromosomes has yet to be exhaustively analyzed. In this study, we explored how pervasive X–Y gene conversion has been during the evolution of the youngest stratum of the human sex chromosomes. By comparing about 0.5 Mb of human–chimpanzee gametologous sequences, we identified 19 regions in which extensive gene conversion has occurred. From our analysis, two major features of these emerged: 1) Several of them are evolutionarily conserved between the two species and 2) almost all of the 19 hotspots overlap with regions where X–Y crossing-over has been previously reported to be involved in sex reversal. Furthermore, in order to explore the dynamics of X–Y gametologous conversion in recent human evolution, we resequenced these 19 hotspots in 68 widely divergent Y haplogroups and used publicly available single nucleotide polymorphism data for the X chromosome. We found that at least ten hotspots are still active in humans. Hence, the results of the interspecific analysis are consistent with the hypothesis of widespread reticulate evolution within gametologous sequences in the differentiation of hominini sex chromosomes. In turn, intraspecific analysis demonstrates that X–Y gene conversion may modulate human sex-chromosome-sequence evolution to a greater extent than previously thought. PMID:24817545
2010-01-01
Background Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic α-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic α-helical domains, and tested these for antiviral and antibacterial activity. Results Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170) - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367) dp (apoBdp), the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W. Conclusions These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of apolipoprotein J has antiviral activity comparable with that for the previously reported apolipoprotein AI derived peptide 18A, suggests that full-length apolipoprotein J may also have such activity, as has been reported for full-length apolipoprotein AI. Although the strength of the anti-infective activity of the sequences identified was limited, this could be increased substantially by developing related mutant peptides. Indeed the apolipoprotein B-derived peptide mutants uncovered by the present study may have utility as HIV therapeutics or microbicides. PMID:20298574
Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China
Ke, Changwen; Mok, Chris Ka Pun; Zhu, Wenfei; Zhou, Haibo; He, Jianfeng; Guan, Wenda; Wu, Jie; Song, Wenjun; Wang, Dayan; Liu, Jiexiong; Lin, Qinhan; Chu, Daniel Ka Wing; Yang, Lei; Zhong, Nanshan; Peiris, Joseph Sriyal Malik
2017-01-01
The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient’s adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread. PMID:28580899
Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.
Fan, Q R; Long, E O; Wiley, D C
2001-05-01
Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits charge and shape complementarity. Specificity is mediated by a pocket in KIR2DL1 that hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids that differ between human and chimpanzee KIRs with HLA-C specificities form solvent-accessible clusters outside the KIR-HLA interface, which suggests undiscovered interactions by KIRs.
Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.
Takeda, Hiroki; Hosoya, Makoto; Fujioka, Masato; Saegusa, Chika; Saeki, Tsubasa; Miwa, Toru; Okano, Hideyuki; Minoda, Ryosei
2018-01-31
There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.
Case report of a p16INK4A-positive branchial cleft cyst.
McLean, T; Iseli, C; Amott, D; Taylor, M
2015-06-01
To report the occurrence of a concurrent oropharyngeal papilloma and branchial cleft cyst linked by p16(INK4A) and human papillomavirus immunohistochemistry. A 42-year-old woman presented with a 1-month history of a left lateral neck mass. Contrast enhanced computed tomography showed a hypodense lesion 20 mm in diameter anteromedial to the left sternocleidomastoid muscle. Ultrasound-guided fine needle aspiration suggested a branchial cleft cyst. Panendoscopy was performed at the time of neck mass removal, and a papillomatous lesion was removed from the left hypopharynx. Histopathological analysis showed the neck lesion to be a branchial cyst containing lymphoid tissue, and the oral lesion to be a squamous papilloma. Immunohistochemical analysis showed both the branchial cleft cyst and papilloma to be positive for p16(INK4A) expression and human papillomavirus DNA. Histological and immunohistochemical analyses support the cystic transformation of lymph nodes, or the 'Inclusion Theory', as the aetiology of branchial apparatus anomalies, and raise the possibility that human papillomavirus infection may play a much larger role in disease of the head and neck than previously supposed.
Annand, E J; Reid, P A
2014-09-01
The first two confirmed cases of Australian bat lyssavirus (ABLV) infection in horses are presented. Both cases occurred in the same week in May 2013 in paddock mates in south-east Queensland. Australia has been one of only a few countries considered free from rabies-like viruses in domestic animal species. ABLV infection had previously only been confirmed in bats and humans. All three confirmed human cases were fatal, the latest in February 2013. An additional human case of possible abortive infection in 1996 has also been reported. Both equine cases reported here resulted in euthanasia. The risks of infection across other mammalian species are still to be determined. These two equine cases highlight that ABLV should be considered as a differential diagnosis in animals with similar clinical presentations in Australia. There is a need for greater awareness regarding the zoonotic risk, use of personal protective equipment, pre- and post-exposure prophylactic measures and laboratory diagnostic options. The authors recommend ABLV testing for all Australian cases of progressive equine neurological disease. © 2014 Australian Veterinary Association.
2015-01-01
Research outlets are increasingly adopting open data policies as a requisite for publication, including studies with human subjects data. We investigated whether open data policies influence participants’ rate of consent by randomly assigning participants to view consent forms with and without discussion of open data policies. No participants declined to participate, regardless of condition, nor did rates of drop-out vs. completion vary between conditions. Furthermore, no significant change in potential consent rates was reported when participants were openly asked about the influence of open data policies on their likelihood of consent. However, follow-up analyses indicated possible poor attention to consent forms, consistent with previous research. Moreover, thematic analysis of participants’ considerations of open data policy indicated multiple considerations such as concerns regarding confidentiality, anonymity, data security, and study sensitivity. The impact of open data policies on participation raises complex issues at the intersection of ethics and scientific innovation. We conclude by encouraging researchers to consider participants as stakeholders in open data policy and by providing recommendations for open data policies in human subjects research. PMID:25993308
Cummings, Jorden A; Zagrodney, Jessica M; Day, T Eugene
2015-01-01
Research outlets are increasingly adopting open data policies as a requisite for publication, including studies with human subjects data. We investigated whether open data policies influence participants' rate of consent by randomly assigning participants to view consent forms with and without discussion of open data policies. No participants declined to participate, regardless of condition, nor did rates of drop-out vs. completion vary between conditions. Furthermore, no significant change in potential consent rates was reported when participants were openly asked about the influence of open data policies on their likelihood of consent. However, follow-up analyses indicated possible poor attention to consent forms, consistent with previous research. Moreover, thematic analysis of participants' considerations of open data policy indicated multiple considerations such as concerns regarding confidentiality, anonymity, data security, and study sensitivity. The impact of open data policies on participation raises complex issues at the intersection of ethics and scientific innovation. We conclude by encouraging researchers to consider participants as stakeholders in open data policy and by providing recommendations for open data policies in human subjects research.
Shoe-Floor Interactions in Human Walking With Slips: Modeling and Experiments.
Trkov, Mitja; Yi, Jingang; Liu, Tao; Li, Kang
2018-03-01
Shoe-floor interactions play a crucial role in determining the possibility of potential slip and fall during human walking. Biomechanical and tribological parameters influence the friction characteristics between the shoe sole and the floor and the existing work mainly focus on experimental studies. In this paper, we present modeling, analysis, and experiments to understand slip and force distributions between the shoe sole and floor surface during human walking. We present results for both soft and hard sole material. The computational approaches for slip and friction force distributions are presented using a spring-beam networks model. The model predictions match the experimentally observed sole deformations with large soft sole deformation at the beginning and the end stages of the stance, which indicates the increased risk for slip. The experiments confirm that both the previously reported required coefficient of friction (RCOF) and the deformation measurements in this study can be used to predict slip occurrence. Moreover, the deformation and force distribution results reported in this study provide further understanding and knowledge of slip initiation and termination under various biomechanical conditions.
The secretory products of Trichomonas vaginalis decrease fertilizing capacity of mice sperm in vitro
Roh, Jaesook; Lim, Young-Su; Seo, Min-Young; Choi, Yuri; Ryu, Jae-Sook
2015-01-01
Trichomonas vaginalis infection is one of the most prevalent sexually transmitted infections in humans and is now recognized as an important cause of infertility in men. There is little information about the effect of extracellular polymeric substances (EPS) from T. vaginalis on sperm, but previous reports do not provide a conclusive description of the functional integrity of the sperm. To investigate the impact of EPS on the fertilizing capacity of sperm, we assessed sperm motility, acrosomal status, hypo-osmotic swelling, and in vitro fertilization rate after incubating the sperm with EPS in vitro using mice. The incubation of sperm with EPS significantly decreased sperm motility, viability, and functional integrity in a concentration and time-dependent manner. These effects on sperm quality also resulted in a decreased fertilization rate in vitro. This is the first report that demonstrates the direct negative impact of the EPS of T. vaginalis on the fertilization rate of sperm in vitro. However, further study should be performed using human sperm to determine if EPS has similar negative impact on human sperm fertilizing capacity in vitro. PMID:25578937
Isobe, Taichi; Hisamori, Shigeo; Hogan, Daniel J; Zabala, Maider; Hendrickson, David G; Dalerba, Piero; Cai, Shang; Scheeren, Ferenc; Kuo, Angera H; Sikandar, Shaheen S; Lam, Jessica S; Qian, Dalong; Dirbas, Frederick M; Somlo, George; Lao, Kaiqin; Brown, Patrick O; Clarke, Michael F; Shimono, Yohei
2014-01-01
MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. We previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. In this study, we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing complex, activates the canonical WNT signaling pathway in an APC-suppression dependent manner, and activates the expression of miR-150. Enforced expression of miR-142 or miR-150 in normal mouse mammary stem cells resulted in the regeneration of hyperproliferative mammary glands in vivo. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. These results suggest that in some tumors, miR-142 regulates the properties of BCSCs at least in part by activating the WNT signaling pathway and miR-150 expression. DOI: http://dx.doi.org/10.7554/eLife.01977.001 PMID:25406066
Cases of human fascioliasis in India: tip of the iceberg.
Ramachandran, J; Ajjampur, S S R; Chandramohan, A; Varghese, G M
2012-01-01
This report presents two cases of human fascioliasis from different states in India. Although only few cases of human fascioliasis have been reported from India previously, both these cases were encountered within a span of three months at this tertiary care centre. Case 1 had significant symptoms with episodes of fever, abdominal pain and eosiniphilia and underwent multiple diagnostic procedures before the correct diagnosis was reached. Case 2, who had few symptoms, had fascioliasis diagnosed with minimal evaluation. These different presentations seen at two ends of the clinical spectrum of disease along with findings of peripheral eosinophilia, and radiological findings led to a presumptive diagnosis that was then confirmed by microscopic examination of bile. Morphometric analysis of ova from these cases was suggestive of infestation with F. gigantica or a F. gigantica-like hybrid. Both patients were treated with triclabendazole which was imported from Geneva. The need to be aware of the possibility of occurrence of this disease and the inclusion of drugs used for treating the disease, in the Indian drug list, should be emphasized.
Thomson, Vicki A.; Lebrasseur, Ophélie; Austin, Jeremy J.; Hunt, Terry L.; Burney, David A.; Denham, Tim; Rawlence, Nicolas J.; Wood, Jamie R.; Gongora, Jaime; Girdland Flink, Linus; Linderholm, Anna; Dobney, Keith; Larson, Greger; Cooper, Alan
2014-01-01
The human colonization of Remote Oceania remains one of the great feats of exploration in history, proceeding east from Asia across the vast expanse of the Pacific Ocean. Human commensal and domesticated species were widely transported as part of this diaspora, possibly as far as South America. We sequenced mitochondrial control region DNA from 122 modern and 22 ancient chicken specimens from Polynesia and Island Southeast Asia and used these together with Bayesian modeling methods to examine the human dispersal of chickens across this area. We show that specific techniques are essential to remove contaminating modern DNA from experiments, which appear to have impacted previous studies of Pacific chickens. In contrast to previous reports, we find that all ancient specimens and a high proportion of the modern chickens possess a group of unique, closely related haplotypes found only in the Pacific. This group of haplotypes appears to represent the authentic founding mitochondrial DNA chicken lineages transported across the Pacific, and allows the early dispersal of chickens across Micronesia and Polynesia to be modeled. Importantly, chickens carrying this genetic signature persist on several Pacific islands at high frequencies, suggesting that the original Polynesian chicken lineages may still survive. No early South American chicken samples have been detected with the diagnostic Polynesian mtDNA haplotypes, arguing against reports that chickens provide evidence of Polynesian contact with pre-European South America. Two modern specimens from the Philippines carry haplotypes similar to the ancient Pacific samples, providing clues about a potential homeland for the Polynesian chicken. PMID:24639505
Piperaki, Evangelia-Theophano; Spanakos, Gregory; Patsantara, Giannoula; Vassalou, Evdokia; Vakalis, Nikolaos; Tsakris, Athanassios
2011-01-01
Human infection with the parasitic nematode Enterobius vermicularis occurs worldwide, particularly in children. Although its prevalence may exceed 35% in some parts of the world, molecular studies of E. vermicularis in humans are limited. The aim of the present study was to investigate the genetic variation within E. vermicularis in a human population. For this purpose, 77 adhesive tape samples taken from Greek children infested with E. vermicularis were tested. New primers were designed to amplify a segment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of E. vermicularis from adhesive tape samples. Thirty-six amplicons were sequenced and eleven different haplotypes were identified. All sequences clustered within the type previously characterized (type B), only reported to date from captive chimpanzees. To the best of our knowledge, this is the first study of E. vermicularis genotypes from a human population. Copyright © 2011 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Flejter, W.L.; McDaniel, L.D.; Johns, D.
1992-01-01
Cultured cells from individuals afflicted with the genetically heterogeneous autosomal recessive disorder xeroderma pigmentosum (XP) exhibit sensitivity to UV radiation and defective nucleotide excision repair. Complementation of these mutant phenotypes after the introduction of single human chromosomes from repair-proficient cells into XP cells has provided a means of mapping the genes involved in this disease. The authors now report the phenotypic correction of XP cells from genetic complementation group D (XP-D) by a single human chromosome designated Tneo. Detailed molecular characterization of Tneo revealed a rearranged structure involving human chromosomes 16 and 19, including the excision repair cross-complementing 2 (ERCC2)more » gene from the previously described human DNA repair gene cluster at 19q13.2-q13.3. Direct transfer of a cosmid bearing the ERCC2 gene conferred UV resistance to XP-D cells.« less
Development of biomimetic nanocomposites as bone extracellular matrix for human osteoblastic cells.
Bhowmick, Arundhati; Mitra, Tapas; Gnanamani, Arumugam; Das, Manas; Kundu, Patit Paban
2016-05-05
Here, we have developed biomimetic nanocomposites containing chitosan, poly(vinyl alcohol) and nano-hydroxyapatite-zinc oxide as bone extracellular matrix for human osteoblastic cells and characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction. Scanning electron microscopy images revealed interconnected macroporous structures. Moreover, in this study, the problem related to fabricating a porous composite with good mechanical strength has been resolved by incorporating 5wt% of nano-hydroxyapatite-zinc oxide into chitosan-poly(vinyl alcohol) matrix; the present composite showed high tensile strength (20.25MPa) while maintaining appreciable porosity (65.25%). These values are similar to human cancellous bone. These nanocomposites also showed superior water uptake, antimicrobial and biodegradable properties than the previously reported results. Compatibility with human blood and pH was observed, indicating nontoxicity of these materials to the human body. Moreover, proliferation of osteoblastic MG-63 cells onto the nanocomposites was also observed without having any negative effect. Copyright © 2016 Elsevier Ltd. All rights reserved.
Malignant mesothelioma following radiation exposure
DOE Office of Scientific and Technical Information (OSTI.GOV)
Antman, K.H.; Corson, J.M.; Li, F.P.
Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommonmore » cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered.« less
Phencyclidine and violence: clinical and legal issues.
Brecher, M; Wang, B W; Wong, H; Morgan, J P
1988-12-01
Phencyclidine (PCP) abuse has diminished since PCP's intrusion into American culture in the late 1970s. One of its legacies is the assumption that it provokes violent behavior in humans with predictable regularity. This assumption is so accepted that ingestion of the drug both accidentally and knowingly prior to committing a crime has been used as a defense in criminal trials. We reviewed 81 clinical reports of toxicity in humans published chiefly in North American medical journals. We searched for descriptions of violent behavior in these reports and subjected them to the following questions: (1) Was the violent behavior corroborated or only self-reported? (2) Was the presence of PCP confirmed by analysis of bodily fluids or postmortem tissue? (3) Was the presence of other drugs excluded by similar analysis of bodily fluids? We had planned to examine the reports to see whether clinicians sought evidence of previous violent behavior, but such an inquiry was rarely conducted. Of the hundreds of patients described, only three satisfied these criteria. Further, some of the papers offered evidence that reports of violence were exaggerated. These findings plus the pre-1970 prospective evaluation of thousands of patients with PCP, in which violence was never reported, led us to conclude that clinical and forensic assumptions about PCP and violence are not warranted.
NASA Astrophysics Data System (ADS)
Xiao, Qing; Jackson, Jeffrey J.; Basak, Ashok; Bowler, Joseph M.; Miller, Brian G.; Zakarian, Armen
2013-05-01
The tatanans are members of a novel class of complex sesquilignan natural products recently isolated from the rhizomes of Acorus tatarinowii Schott plants. Tatanans A, B and C have previously been reported to have potent glucokinase-activating properties that exceed the in vitro activity of known synthetic antidiabetic agents. Here, using a series of sequential [3,3]-sigmatropic rearrangements, we report the total synthesis of tatanan A in 13 steps and 13% overall yield. We also complete a concise enantioselective total synthesis of more complex, atropisomeric tatanans B and C via a distinct convergent strategy based on a palladium-catalysed diastereotopic aromatic group differentiation (12 steps, 4% and 8% overall yield, respectively). A plausible biosynthetic relationship between acyclic tatanan A and spirocyclic tatanans B and C is proposed and probed experimentally. With sufficient quantities of the natural products in hand, we undertake a detailed functional characterization of the biological activities of tatanans A-C. Contrary to previous reports, our assays utilizing pure recombinant human enzyme demonstrate that tatanans do not function as allosteric activators of glucokinase.
Identification of Human Semiochemicals Attractive to the Major Vectors of Onchocerciasis
Young, Ryan M.; Burkett-Cadena, Nathan D.; McGaha, Tommy W.; Rodriguez-Perez, Mario A.; Toé, Laurent D.; Adeleke, Monsuru A.; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R.; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L.; Salinas-Carmona, Mario C.; Baker, Bill; Unnasch, Thomas R.; Cupp, Eddie W.
2015-01-01
Background Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Methodology/Principal Findings Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. Conclusions/Significance The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa. PMID:25569240
Identification of human semiochemicals attractive to the major vectors of onchocerciasis.
Young, Ryan M; Burkett-Cadena, Nathan D; McGaha, Tommy W; Rodriguez-Perez, Mario A; Toé, Laurent D; Adeleke, Monsuru A; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L; Salinas-Carmona, Mario C; Baker, Bill; Unnasch, Thomas R; Cupp, Eddie W
2015-01-01
Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.
Comparative ocular anatomy of the western lowland gorilla.
Knapp, Stefanie; McCulley, James P; Alvarado, Thomas P; Hogan, R Nick
2007-01-01
To examine the lowland gorilla (Gorilla gorilla gorilla) eye and determine similarities to and differences between the mountain gorilla (Gorilla gorilla beringei) and the human eye. In addition, we compare our findings of G. g. gorilla to previous reports on the eye of this subspecies. A 13-year-old deceased male lowland gorilla and a 34-year-old deceased female lowland gorilla were included in the study. Gross and microscopic examinations of the formalin-fixed right eyeball of each gorilla were carried out. Globe dimensions of G. g. gorilla were similar to G. g. beringei and to humans. The limbal conjunctival epithelium and the choroid were densely pigmented. However, the distribution of the conjunctival pigment ring was different to that of G. g. beringei and the melanocytes of the choroid were unusually round. There were deep crypts in the anterior border layer of the iris, and the epithelium of the pars plana was uniquely irregular. Vertical corneal diameter was observed to be equal or greater than horizontal diameter in G. g. gorilla, which is in contrast to humans and to previous findings for G. g. beringei. Corneal thickness was closer to that of humans than to G. g. beringei. Posterior lens capsule thickness was noticeably greater than that of humans. Although some variation between the ocular anatomy of G. g. gorilla and G. g. beringei does exist, the gross and microscopic findings closely resemble each other in these two subspecies. In addition, the eye of Gorilla appears remarkably similar to the human eye. However, comparison of measurements with those in humans is somewhat limited because formalin-fixation can introduce tissue shrinkage and artifact.
Primary urinary bladder haemangiosarcoma in a captive saddleback tamarin (Saguinus fuscicollis).
Gonzales-Viera, Omar; Quevedo, Tatiana; Chavera, Alfonso; Perales-Camacho, Rosa; Grandi, Fabrizio; Catão-Dias, José L
2014-08-01
A captive adult male saddleback tamarin, Saguinus fuscicollis, was lethargic, unresponsive to its surrounding and died before medical care. Necroscopic, histopathological and immunohistochemical examinations were performed. Neoplastic spindle cells of the urinary bladder were positive for antifactor VIII antibody. A primary urinary bladder haemangiosarcoma was diagnosed, and it has not been previously reported in non-human primates. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Selection and Characterization of Drug-Resistant Variants of Human Immunodeficiency Virus (AIDS).
1995-10-01
on Antiviral Reserach, Santa Fe, New Mexico , 1995. Page 18 APPENDIX Page 19 p - FACTFILE Mutations in HIV-1 Reverse Transcriptase and Protease...including herpes simplex viruses, varicella -zoster Resistance of clinical HIV-1 isolates to foscarnet has not virus, cytomegalovirus (CMV), hepatitis B...This effect of the Tyr-208 substitution was not ob- reported previously for herpes simplex viruses, varicella -zoster served in MT-2 cells, however. virus
Extending and Applying the EPIC Architecture for Human Cognition and Performance
2011-01-01
for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. and to the Office of Management and...already underway in the previous project, and then moving on to some other topics. However, it became clear that providing an adequate account of visual...search was in fact an extremely challenging project all by itself. Very few cognitive modeling projects have attempted to account for such a span of
Lognormal Infection Times of Online Information Spread
Doerr, Christian; Blenn, Norbert; Van Mieghem, Piet
2013-01-01
The infection times of individuals in online information spread such as the inter-arrival time of Twitter messages or the propagation time of news stories on a social media site can be explained through a convolution of lognormally distributed observation and reaction times of the individual participants. Experimental measurements support the lognormal shape of the individual contributing processes, and have resemblance to previously reported lognormal distributions of human behavior and contagious processes. PMID:23700473
2014-01-01
Defence Force Bonnie R. Tran Anne G. Thomas David Kelapile Florin Vaida Richard Haubrich Mooketsi Ditsela Christina Chambers Robert...intervention Introduction Military personnel are at increased risk for human immunodeficiency virus (HIV) and other sexually trans - mitted infections (STIs...and post-intervention focus groups. Results from the baseline and post-intervention surveys are previously reported ( Tran , Thomas, Ditsela, et al
Wermuth, Peter J; Jimenez, Sergio A
2012-07-01
Nephrogenic systemic sibrosis is a progressive disorder occurring in some renal insufficiency patients exposed to gadolinium-based contrast agents (GdBCA). Previous studies demonstrated that the GdBCA Omniscan upregulated several innate immunity pathways in normal differentiated human macrophages, induced rapid nuclear localization of the transcription factor NF-κB, and increased the expression and production of numerous profibrotic/proinflammatory cytokines, chemokines, and growth factors. To further examine GdBCA stimulation of the innate immune system, cultured human embryonic kidney 293 cells expressing one of seven different human TLRs or one of two human nucleotide-binding oligomerization domain-like receptors were exposed in vitro for 24 h to various GdBCA. The signaling activity of each compound was evaluated by its ability to activate an NF-κB-inducible reporter gene. Omniscan and gadodiamide induced strong TLR4- and TLR7-mediated reporter gene activation. The other Gd compounds examined failed to induce reporter gene activation. TLR pathway inhibition using chloroquine or an inhibitor of IL-1R-associated kinases 1 and 4 in normal differentiated human macrophages abrogated Omniscan-induced gene expression. Omniscan and gadodiamide signaling via TLRs 4 and 7 resulted in increased production and expression of numerous proinflammatory/profibrotic cytokines, chemokines, and growth factors, including CXCL10, CCL2, CCL8, CXCL12, IL-4, IL-6, TGF-β, and vascular endothelial growth factor. These observations suggest that TLR activation by environmental stimuli may participate in the pathogenesis of nephrogenic systemic fibrosis and of other fibrotic disorders including systemic sclerosis.
In-Vitro Archaeacidal Activity of Biocides against Human-Associated Archaea
Khelaifia, Saber; Michel, Jean Brunel; Drancourt, Michel
2013-01-01
Background Several methanogenic archaea have been detected in the human intestinal microbiota. These intestinal archaea may contaminate medical devices such as colonoscopes. However, no biocide activity has been reported among these human-associated archaea. Methodology The minimal archaeacidal concentration (MAC) of peracetic acid, chlorhexidine, squalamine and twelve parent synthetic derivatives reported in this study was determined against five human-associated methanogenic archaea including Methanobrevibacter smithii, Methanobrevibacter oralis, Methanobrevibacter arboriphilicus, Methanosphaera stadtmanae, Methanomassiliicoccus luminyensis and two environmental methanogens Methanobacterium beijingense and Methanosaeta concilii by using a serial dilution technique in Hungates tubes. Principal Findings MAC of squalamine derivative S1 was 0.05 mg/L against M. smithii strains, M. oralis, M. arboriphilicus, M. concilii and M. beijingense whereas MAC of squalamine and derivatives S2–S12 varied from 0.5 to 5 mg/L. For M. stadtmanae and M. luminyensis, MAC of derivative S1 was 0.1 mg/L and varied from 1 to ≥10 mg/L for squalamine and its parent derivatives S2–S12. Under the same experimental conditions, chlorhexidine and peracetic acid lead to a MAC of 0.2 and 1.5 mg/L, respectively against all tested archaea. Conclusions/Significance Squalamine derivative S1 exhibited a 10–200 higher archaeacidal activity than other tested squalamine derivatives, on the majority of human-associated archaea. As previously reported and due to their week corrosivity and their wide spectrum of antibacterial and antifungal properties, squalamine and more precisely derivative S1 appear as promising compounds to be further tested for the decontamination of medical devices contaminated by human-associated archaea. PMID:23658767
Integrated Human Surveillance Systems of West Nile Virus Infections in Italy: The 2012 Experience
Napoli, Christian; Bella, Antonino; Declich, Silvia; Grazzini, Giuliano; Lombardini, Letizia; Nanni Costa, Alessandro; Nicoletti, Loredana; Pompa, Maria Grazia; Pupella, Simonetta; Russo, Francesca; Rizzo, Caterina
2013-01-01
In Italy, a West Nile virus (WNV) surveillance plan was firstly implemented in 2008 and 2009 in two affected regions and, since 2010, according to a national plan, a WNV neuroinvasive disease (WNND) surveillance has to be carried out each year during the period 15 June–30 November, in those regions where WNV circulation has been demonstrated among humans, animals or vectors. Moreover, since WNV can be transmitted to humans even by blood transfusions and organ transplants obtained from infected donors, the national surveillance integrates the blood transfusions and organs transplant surveillances too. The paper describes the results of this integrated human surveillance in Italy in 2012. Overall, in 2012, 28 autochthonous confirmed cases of WNND were reported, 14 blood donations were found WNV positive by Nucleic Acid Amplification Test and no solid organ donors tested positive for WNV. Moreover, 17 cases of WNV fever were confirmed in Veneto region. When comparing the number of WNND cases reported to the surveillance system in previous 4 years (43 cases during the period 2008–2011), with those reported in 2012 an important increase was observed in 2012. The geographic distribution of human cases was consistent with the WNV circulation among animals and vectors. Moreover, the implementation of preventive measures for WNV transmission through blood components allowed the detection of blood donors positive for WNV, avoiding the further spread of the disease. Since surveillance strategies and preventive measures are based on the integration among human, animal and vector control activities, the Italian experience could be considered a good example of collaboration among different sectors of public health in a “one health” perspective. PMID:24351740
Corrêa, Natássia Caroline Resende; Kuligovski, Crisciele; Paschoal, Ariane Caroline Campos; Abud, Ana Paula Ressetti; Rebelatto, Carmen Lucia Kuniyoshi; Leite, Lidiane Maria Boldrini; Senegaglia, Alexandra Cristina; Dallagiovanna, Bruno; Aguiar, Alessandra Melo de
2018-02-01
With the increasing need to develop in vitro assays to replace animal use, human stem cell-derived methods are emerging and showing outstanding contributions to the toxicological screening of substances. Adult human stem cells such as adipose-derived stem cells (ADSC) and periodontal ligament stem cells (PDLSC) were used as cell substrates for a cytotoxicity assay and toxicity prediction using the neutral red uptake (NRU) assay. First, primary cell cultures from three independent donors, from each tissue source, were characterized as mesenchymal stem cells (MSC) by plastic adherence and appropriate immunophenotype for MSC markers (positive for CD90, CD73, and CD105 and negative for CD11b, CD34, CD45, HLADR, and CD19). Furthermore, ADSC and PDLSC were able to differentiate into adipocytes and osteoblasts when maintained under the same culture conditions previously established for the NRU assay. NRU assays for three reference test substances were performed. R 2 was higher than 0.85 for all conditions, showing the feasibility to calculate IC 50 values. The IC 50 values were then used to predict the LD 50 of the test substances, which were comparable to previous results and the ICCVAM standard test report. Primary ADSC and PDLSC showed the potential to be considered as additional models for use in cytotoxicity assays. Copyright © 2017 Elsevier Inc. All rights reserved.
Starch grains on human teeth reveal early broad crop diet in northern Peru
Piperno, Dolores R.; Dillehay, Tom D.
2008-01-01
Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 14C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 14C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Ñanchoc region by 8000 14C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture. PMID:19066222
SETD2 is recurrently mutated in whole-exome sequenced canine osteosarcoma.
Sakthikumar, Sharadha; Elvers, Ingegerd; Kim, Jaegil; Arendt, Maja L; Thomas, Rachael; Turner-Maier, Jason; Swofford, Ross; Johnson, Jeremy; Schumacher, Steven E; Alföldi, Jessica; Axelsson, Erik; Couto, Guillermo; Kisseberth, William; Pettersson, Mats E; Getz, Gad; Meadows, Jennifer R S; Modiano, Jaime F; Breen, Matthew; Kierczak, Marcin; Forsberg-Nilsson, Karin; Marinescu, Voichita D; Lindblad-Toh, Kerstin
2018-05-03
Osteosarcoma (OSA) is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of OSA spontaneously occurs in dogs, and its differential incidence observed across breeds allows for the investigation of tumor mutations in the context of multiple genetic backgrounds. Using whole-exome sequencing and dogs from three susceptible breeds (22 golden retrievers, 21 Rottweilers, and 23 greyhounds), we found that OSA tumors show a high frequency of somatic copy number alterations (SCNA) affecting key oncogenes and tumor suppressor genes. The across-breed results are similar to what has been observed for human OSA, but the disease frequency and somatic mutation counts vary in the three breeds. For all breeds, three mutational signatures (one of which has not been previously reported), and eleven significantly mutated genes were identified. TP53 was the most frequently altered gene (83% of dogs have either mutations or SCNA in TP53), recapitulating observations in human OSA. The second most frequently mutated gene, histone methyltransferase SETD2, has known roles in multiple cancers, but has not previously been strongly implicated in OSA. This study points to the likely importance of histone modifications in OSA and highlights the strong genetic similarities between human and dog OSA, suggesting that canine OSA may serve as an excellent model for developing treatment strategies in both species. Copyright ©2018, American Association for Cancer Research.
Petri, Anne-Kathrin; Schmiedchen, Kristina; Stunder, Dominik; Dechent, Dagmar; Kraus, Thomas; Bailey, William H; Driessen, Sarah
2017-04-17
High-voltage direct current (HVDC) lines are the technology of choice for the transport of large amounts of energy over long distances. The operation of these lines produces static electric fields (EF), but the data reviewed in previous assessments were not sufficient to assess the need for any environmental limit. The aim of this systematic review was to update the current state of research and to evaluate biological effects of static EF. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations, we collected and evaluated experimental and epidemiological studies examining biological effects of exposure to static EF in humans (n = 8) and vertebrates (n = 40). There is good evidence that humans and animals are able to perceive the presence of static EF at sufficiently high levels. Hair movements caused by electrostatic forces may play a major role in this perception. A large number of studies reported responses of animals (e.g., altered metabolic, immunologic or developmental parameters) to a broad range of static EF strengths as well, but these responses are likely secondary physiological responses to sensory stimulation. Furthermore, the quality of many of the studies reporting physiological responses is poor, which raises concerns about confounding. The weight of the evidence from the literature reviewed did not indicate that static EF have adverse biological effects in humans or animals. The evidence strongly supported the role of superficial sensory stimulation of hair and skin as the basis for perception of the field, as well as reported indirect behavioral and physiological responses. Physical considerations also preclude any direct effect of static EF on internal physiology, and reports that some physiological processes are affected in minor ways may be explained by other factors. While this literature does not support a level of concern about biological effects of exposure to static EF, the conditions that affect thresholds for human detection and possible annoyance at suprathreshold levels should be investigated.
Feltus, F Alex; Kovacs, William J; Nicholson, Wendell; Silva, Corrine M; Nagdas, Subir K; Ducharme, Nicole A; Melner, Michael H
2003-05-01
We tested the ability of epidermal growth factor (EGF) to regulate a key enzyme in the adrenal synthesis of glucocorticoids: human type II 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3 beta HSD). EGF treatment (25 ng/ml) of human adrenocortical carcinoma cells (H295R) resulted in a 5-fold increase in cortisol production and a corresponding 2-fold increase in 3 beta HSD mRNA. Experiments were performed to determine whether EGF is acting through a previously identified signal transducer and activator of transcription 5 (Stat5)-responsive element located from -110 to -118 in the human type II 3 beta HSD promoter. A Stat5 expression construct was cotransfected with a 3 beta HSD-chloramphenol acetyltransferase (CAT) reporter construct comprised of nucleotides -301-->+45 of the human type II 3 beta HSD promoter linked to the CAT reporter gene sequence. The addition of EGF at doses as low as 10 ng/ml resulted in an 11- to 15-fold increase in CAT activity. The introduction of 3-bp point mutations into critical nucleotides in the Stat5 response element obviated the EGF response. Either Stat5a or Stat5b isoforms induced CAT reporter expression upon treatment with EGF. These results demonstrate the ability of EGF to regulate the expression of a critical enzyme (3 beta HSD) in the production of cortisol and suggest a molecular mechanism by which this regulation occurs.
Social group dynamics predict stress variability among children in a New Zealand classroom.
Spray, Julie; Floyd, Bruce; Littleton, Judith; Trnka, Susanna; Mattison, Siobhan
2018-03-27
Previous research proposes stress as a mechanism for linking social environments and biological bodies. In particular, non-human primate studies investigate relationships between cortisol as a measure of stress response and social hierarchies. Because human social structures often include hierarchies of dominance and social status, humans may exhibit similar patterns. Studies of non-human primates, however, have not reached consistent conclusions with respect to relationships between social position and levels of cortisol. While human studies report associations between cortisol and various aspects of social environments, studies that consider social status as a predictor of stress response also report mixed results. Others have argued that perceptions of social status may have different implications for stress response depending upon social context. We propose here that characteristics of children's social networks may be a better predictor of central tendencies and variability of stress response than their perceptions of social status. This is evaluated among 24 children from 9.4 to 11.3 years of age in one upper middle-class New Zealand primary school classroom, assessed through observation within the classroom, self-reports during semi-structured interviews and 221 serial saliva samples provided daily over 10 consecutive school days. A synthetic assessment of the children's networks and peer-relationships was developed prior to saliva-cortisol analysis. We found that greater stability of peer-relationships within groups significantly predicts lower within-group variation in mid-morning cortisol over the two-week period, but not overall within-group differences in mean cortisol. Copyright © 2018 Elsevier GmbH. All rights reserved.
NASA Astrophysics Data System (ADS)
Arkwright, J. W.; Blenman, N. G.; Underhill, I. D.; Maunder, S. A.; Spencer, N. J.; Costa, M.; Brooks, S. J.; Szczesniak, M. M.; Dinning, P. G.
2010-09-01
Diagnostic catheters based on fibre Bragg gratings (FBG's) are proving to be highly effective for measurement of the muscular activity associated with peristalsis in the human gut. The primary muscular contractions that generate peristalsis are circumferential in nature; however, it has long been known that there is also a component of longitudinal contractility present, acting in harmony with the circumferential component to improve the overall efficiency of material movement. To date, there have been relatively few reports on the measurement or inference of longitudinal contractions in humans and all have been limited to detection at a single location only. This is due to the lack of a viable recording technique suitable for real-time in-vivo measurement of this type of activity over extended lengths of the gut. We report the detection of longitudinal motion in lengths of excised mammalian colon using an FBG technique that should be viable for similar detection in humans. The longitudinal sensors have been combined with our previously reported FBG pressure sensing elements to form a composite catheter that allows the relative phase between the two components to be detected. The catheter output has been validated using digital video mapping in an ex-vivo animal preparation using lengths of rabbit ileum.
Simultaneous atelectasis in human bocavirus infected monozygotic twins: was it plastic bronchitis?
Rüegger, Christoph M; Bär, Walter; Iseli, Peter
2013-12-18
Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children. We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus. Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants.
Simultaneous atelectasis in human bocavirus infected monozygotic twins: was it plastic bronchitis?
2013-01-01
Background Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children. Case presentation We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus. Conclusion Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants. PMID:24344641
Developmental Testing of Habitability and Human Factors Tools and Methods During Neemo 15
NASA Technical Reports Server (NTRS)
Thaxton, S. S.; Litaker, H. L., Jr.; Holden, K. L.; Adolf, J. A.; Pace, J.; Morency, R. M.
2011-01-01
Currently, no established methods exist to collect real-time human factors and habitability data while crewmembers are living aboard the International Space Station (ISS), traveling aboard other space vehicles, or living in remote habitats. Currently, human factors and habitability data regarding space vehicles and habitats are acquired at the end of missions during postflight crew debriefs. These debriefs occur weeks or often longer after events have occurred, which forces a significant reliance on incomplete human memory, which is imperfect. Without a means to collect real-time data, small issues may have a cumulative effect and continue to cause crew frustration and inefficiencies. Without timely and appropriate reporting methodologies, issues may be repeated or lost. TOOL DEVELOPMENT AND EVALUATION: As part of a directed research project (DRP) aiming to develop and validate tools and methods for collecting near real-time human factors and habitability data, a preliminary set of tools and methods was developed. These tools and methods were evaluated during the NASA Extreme Environments Mission Operations (NEEMO) 15 mission in October 2011. Two versions of a software tool were used to collect observational data from NEEMO crewmembers that also used targeted strategies for using video cameras to collect observations. Space habitability observation reporting tool (SHORT) was created based on a tool previously developed by NASA to capture human factors and habitability issues during spaceflight. SHORT uses a web-based interface that allows users to enter a text description of any observations they wish to report and assign a priority level if changes are needed. In addition to the web-based format, a mobile Apple (iOS) format was implemented, referred to as iSHORT. iSHORT allows users to provide text, audio, photograph, and video data to report observations. iSHORT can be deployed on an iPod Touch, iPhone, or iPad; for NEEMO 15, the app was provided on an iPad2.
Shen, C; Meng, Q; Zhang, G; Hu, W
2007-01-01
Background and purpose: Rifampicin has been extensively reported to exacerbate the hepatotoxicity of isoniazid in patients with tuberculosis. However, this was controversially claimed by previous reports using rat models. This study evaluated the effect of rifampicin on isoniazid-induced hepatocyte toxicity by using human and rat hepatocytes in tissue-like culture. Experimental approach: Hepatocytes in tissue-like gel entrapment were used to examine isoniazid toxicity, as shown by cell viability, intracellular glutathione content and albumin secretion. For demonstration of the differential effects of rifampicin on human and rat hepatocytes, induction by rifampicin of cytochrome P450 (CYP) 2E1, a major enzyme associated with isoniazid hepatotoxicity, was detected by 4-nitrocatechol formation and RT-PCR analysis. Key results: Rifampicin (12 μM) enhanced isoniazid-induced toxicity in human hepatocytes but not in rat hepatocytes. Enhanced CYP 2E1 enzymic activity and mRNA expression were similarly detected in human hepatocytes but not in rat hepatocytes. Both rat and human hepatocytes in gel entrapment were more sensitive to isoniazid treatment compared with the corresponding hepatocytes in a monolayer culture. Conclusions and implications: The difference in induction of CYP 2E1 by rifampicin between rat and human hepatocytes accounted for the difference in exacerbation of isoniazid hepatocyte toxicity by rifampicin, with more significant toxicity in gel entrapment than in monolayer cultures. Thus, human hepatocytes in tissue-like cultures (gel entrapment) could be an effective model for hepatotoxicity research in vitro, closer to the in vivo situation. PMID:18071298