Cell biology solves mysteries of reproduction

Reproduction and fertility have been objects of keen inquiry since the dawn of humanity. Medieval anatomists provided the first accurate depictions of the female reproductive system, and early microscopists were fascinated by the magnified sight of sperm cells. Initial successes were achieved in the in vitro fertilization of frogs and the artificial insemination of dogs. Gamete and embryo research was in the cradle of modern cell biology, providing the first evidence of the multi-cellular composition of living beings and pointing out the importance of chromosomes for heredity. In the 20th century, reproductive research paved the way for the study of the cytoskeleton, cell signaling, and the cell cycle. In the last three decades, the advent of reproductive cell biology has brought us human in vitro fertilization, animal cloning, and human and animal embryonic stem cells. It has contributed to the development of transgenesis, proteomics, genomics, and epigenetics. This Special Issue represents a sample of the various areas of reproductive biology, with emphasis on molecular and cell biological aspects. Advances in spermatology, ovarian function, fertilization, and maternal-fetal interactions are discussed within the framework of fertility and diseases such as endometriosis and diabetes.     

The Risks of Yellow Fever to Asian Primates

International Journal of Primatology - Infectious diseases are a growing threat to the conservation of nonhuman primates. In the case of diseases shared with humans, the risk is higher where...     

The effect of adjuvants on vaccine-induced antibody response against influenza in aged mice

While influenza remains a major threat to public health, researchers continue to search for a universal solution to improving the efficacy of the influenza vaccine. Even though influenza affects people of all different ages, it can be extremely hazardous to people of 65 years of age or older since that is the population that makes up the high majority of the death toll caused by influenza-related diseases. Elderly individuals suffer the effects of immunosenescence as they age, which is the diminishing of the overall immune response. Immunosenescence occurs by specifically affecting the adaptive immune response which controls the establishment of immunity after vaccination or infection. There are many studies under way that are trying to find a resolution to the problem of the influenza vaccine not providing enough protection in the elderly population. One of the possible strategies is to seek the use of an optimal adjuvant, an immunological agent that can enhance immune responses, with the current vaccine formulation. Here, we used the murine model to review the effects of adjuvants on the antibody response to influenza vaccines in aged mice. Since adjuvants can enhance the production of important inflammatory cytokines and activation of dendritic cells, the stimulation of these cells are boosted to increase the effectiveness of the influenza vaccine in aged mice which would hopefully translate to the elderly.     

Meeting report: How to get wrong things right--a discussion over current and future pandemic infectious diseases

Infectious diseases have played a substantial part in shaping the history of humanity. In a discussion at a recent EMBL-EMBO science and society symposium entitled 'The future of our species', several experts discussed how infectious diseases are still influencing our world today. Here we present examples from recent and current infectious disease epidemics followed by a discussion of the local, national and international response to these. Special emphasis is laid on how the change of our environment can augment the world-wide spread of infectious diseases and the role of education in limiting this spread. An urgent need for improved coordinative efforts in globally combating infectious diseases is called for and examples are highlighted.     

Palaeopathology and genes: Investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations

The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future.     

Do we have a right to an unmanipulated genome? The human genome as the common heritage of mankind

The human genome is commonly regarded as a ‘natural’ connection between all human beings, as it has been handed down to us by our predecessors. As such, it is believed to represent common heritage of humanity, e.g. a resource of outstanding value that should be the object of special protection and international concern. Some critics argue that germline manipulation would disrupt this natural heritage and that we have a duty to preserve the integrity of the human germline. However, a closer look reveals that the concept of common heritage of humanity does not necessarily imply the impermissibility of germline manipulation. If it is restricted to the prevention of severe diseases, germline manipulation does not represent a threat to the unity and identity of the human species, even though this would create a new form of relationship between human beings, namely that between a designer and a genetically designed person.     

Forecasting the 2013–2014 Influenza Season Using Wikipedia

Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.     

禽流感:一种人畜共患病

禽流感 (AvianInfluenza ,AI)是严重危害畜牧业与人类健康的一种传染性疾病。多年来在世界上许多国家和地区都发生过此病 ,危害严重 ,经济损失巨大。禽流感病毒可感染多种动物 ,包括人、猪、马、鲸、海豹和雪貂。禽流感病毒经变异或基因重组 ,已具备感染人的能力 ,有可能成为人类新型流感流行的潜在病原。本文对与禽流感病毒相关的流感疫情进行历史性的回顾 ,并对其人畜共患机制做了初步探讨     

The Leeuwenhoek Lecture 2001. Animal origins of human infectious disease

Since time immemorial animals have been a major source of human infectious disease. Certain infections like rabies are recognized as zoonoses caused in each case by direct animal-to-human transmission. Others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. Recent examples of direct zoonoses are variant Creutzfeldt-Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Epidemics of recent animal origin are the 1918-1919 influenza pandemic, and acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV). Some retroviruses jump into and out of the chromosomal DNA of the host germline, so that they oscillate between being inherited Mendelian traits or infectious agents in different species. Will new procedures like animal-to-human transplants unleash further infections? Do microbes become more virulent upon cross-species transfer? Are animal microbes a threat as biological weapons? Will the vast reservoir of immunodeficient hosts due to the HIV pandemic provide conditions permissive for sporadic zoonoses to take off as human-to-human transmissible diseases? Do human infections now pose a threat to endangered primates? These questions are addressed in this lecture.     

Clinical Profiles Associated with Influenza Disease in the Ferret Model

Influenza A viruses continue to pose a threat to human health; thus, various vaccines and prophylaxis continue to be developed. Testing of these products requires various animal models including mice, guinea pigs, and ferrets. However, because ferrets are naturally susceptible to infection with human influenza viruses and because the disease state resembles that of human influenza, these animals have been widely used as a model to study influenza virus pathogenesis. In this report, a statistical analysis was performed to evaluate data involving 269 ferrets infected with seasonal influenza, swine influenza, and highly pathogenic avian influenza (HPAI) from 16 different studies over a five year period. The aim of the analyses was to better qualify the ferret model by identifying relationships among important animal model parameters (endpoints) and variables of interest, which include survival, time-to-death, changes in body temperature and weight, and nasal wash samples containing virus, in addition to significant changes from baseline in selected hematology and clinical chemistry parameters. The results demonstrate that a disease clinical profile, consisting of various changes in the biological parameters tested, is associated with various influenza A infections in ferrets. Additionally, the analysis yielded correlates of protection associated with HPAI disease in ferrets. In all, the results from this study further validate the use of the ferret as a model to study influenza A pathology and to evaluate product efficacy.     

Influenza virus-specific cytotoxic T lymphocytes: a correlate of protection and a basis for vaccine development

Since influenza A viruses of the H5N1 subtype continue to circulate in wild and domestic birds and cause an ever increasing number of human cases, it is feared that H5N1 viruses may cause the next influenza pandemic. Therefore, there is considerable interest in the development of vaccines that confer protection against infections with these viruses or ideally, protection against influenza viruses of different subtypes. For the development of broad-protective vaccines the induction of virus-specific cytotoxic T lymphocytes (CTL) may be an important target, since it has been demonstrated that CTL contribute to protective immunity and are largely directed to epitopes shared by influenza viruses of various subtypes. In the present paper, the possibility to develop (cross-reactive) CTL-inducing vaccines is discussed.     

Adaptation of Pandemic H2N2 Influenza A Viruses in Humans

The 1957 A/H2N2 influenza virus caused an estimated 2 million fatalities during the pandemic. Since viruses of the H2 subtype continue to infect avian species and pigs, the threat of reintroduction into humans remains. To determine factors involved in the zoonotic origin of the 1957 pandemic, we performed analyses on genetic sequences of 175 newly sequenced human and avian H2N2 virus isolates and all publicly available influenza virus genomes.     

Prediction of Directional Changes of Influenza A Virus Genome Sequences with Emphasis on Pandemic H1N1/09 as a Model Case

Influenza virus poses a significant threat to public health, as exemplified by the recent introduction of the new pandemic strain H1N1/09 into human populations. Pandemics have been initiated by the occurrence of novel changes in animal sources that eventually adapt to human. One important issue in studies of viral genomes, particularly those of influenza virus, is to predict possible changes in genomic sequence that will become hazardous. We previously established a clustering method termed ‘BLSOM’ (batch-learning self-organizing map) that does not depend on sequence alignment and can characterize and compare even 1 million genomic sequences in one run. Strategies for comparing a vast number of genomic sequences simultaneously become increasingly important in genome studies because of remarkable progresses in nucleotide sequencing. In this study, we have constructed BLSOMs based on the oligonucleotide and codon composition of all influenza A viral strains available. Without prior information with regard to their hosts, sequences derived from strains isolated from avian or human sources were successfully clustered according to the hosts. Notably, the pandemic H1N1/09 strains have oligonucleotide and codon compositions that are clearly different from those of human seasonal influenza A strains. This enables us to infer future directional changes in the influenza A viral genome.     

人类与病原菌的军备竞赛:NDM-1耐药基因与超级细菌

在人类历史上,每一次诸如鼠疫和肺结核病等瘟疫的大流行,都曾给人类的生存带来巨大的威胁。抗生素的应用使人类掌握了抵抗细菌感染的锐利"武器",但同时病原菌也通过突变和水平基因转移等方式产生了诸多耐药基因,从而获得了应对抗生素杀伤的坚固"盾牌";于是人类又不断地开发新式抗生素"武器"来破解病原菌的耐药"盾牌"——一场"军备竞赛"愈演愈烈。近来研究发现,携带编码NDM-1基因的耐药质粒不仅可以在细菌间转移,而且能使所在宿主菌成为可以耐受几乎全部抗生素的超级细菌。但是,凭借着日益进步的科技和医学,以及科学的用药策略,我们一定可以再次战胜超级细菌。     

Distinct Host Tropism Protein Signatures to Identify Possible Zoonotic Influenza A Viruses

Zoonotic influenza A viruses constantly pose a health threat to humans as novel strains occasionally emerge from the avian population to cause human infections. Many past epidemic as well as pandemic strains have originated from avian species. While most viruses are restricted to their primary hosts, zoonotic strains can sometimes arise from mutations or reassortment, leading them to acquire the capability to escape host species barrier and successfully infect a new host. Phylogenetic analyses and genetic markers are useful in tracing the origins of zoonotic infections, but there are still no effective means to identify high risk strains prior to an outbreak. Here we show that distinct host tropism protein signatures can be used to identify possible zoonotic strains in avian species which have the potential to cause human infections. We have discovered that influenza A viruses can now be classified into avian, human, or zoonotic strains based on their host tropism protein signatures. Analysis of all influenza A viruses with complete proteome using the host tropism prediction system, based on machine learning classifications of avian and human viral proteins has uncovered distinct signatures of zoonotic strains as mosaics of avian and human viral proteins. This is in contrast with typical avian or human strains where they show mostly avian or human viral proteins in their signatures respectively. Moreover, we have found that zoonotic strains from the same influenza outbreaks carry similar host tropism protein signatures characteristic of a common ancestry. Our results demonstrate that the distinct host tropism protein signature in zoonotic strains may prove useful in influenza surveillance to rapidly identify potential high risk strains circulating in avian species, which may grant us the foresight in anticipating an impending influenza outbreak.     

Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is an acute infectious disease caused by CCHF virus (CCHFV), a member of the family Bunyaviridae, genus Nairovirus. The case fatality rate of CCHF ranges from 10-40%. Because CCHF is not present in Japan, many Japanese virologists and clinicians are not very familiar with this disease. However, there remains the possibility of an introduction of CCHFV or other hemorrhagic fever viruses into Japan from surrounding endemic areas. Development of diagnostic laboratory capacity for viral hemorrhagic fevers is necessary even in countries without these diseases. At the National Institute of Infectious Diseases, Tokyo, Japan, laboratory-based systems such as recombinant protein-based antibody detection, antigen-capture and pathological examination have been developed. In this review article, epidemiologic and clinical data on CCHF in the Xinjiang Uygur Autonomous Region, compiled through field investigations and diagnostic testing utilizing the aforementioned laboratory systems, are presented. CCHFV infections are closely associated with the environmental conditions, life styles, religion, occupation, and human economic activities. Based on these data, preventive measures for CCHFV infections are also discussed.     

The clinico-laboratory characteristics of cases of diseases connected with viruses of the California encephalitis complex in the inhabitants of Moscow

To study the role of viruses of the California encephalitis virus complex (the family Bunyaviridae) in infectious pathology, 187 fever patients admitted to the Clinical Infectious Hospital in May-September 1986 were examined. In 10 of these patients the neutralization test revealed the presence of diagnostically significant changes in neutralizing antibodies (neutralization indices), which was indicative of the role played by Tahyna virus or other related viruses belonging to the California encephalitis virus complex in the etiology of the diseases. The analysis of the clinical picture showed that in all patients the disease took an acute course in its initial stage, starting with shivering and characterized by high fever, headache, pronounced toxicosis, the possibility of the formation of intracerebral hypertension and pneumonia.     

Fever, petechiae, and pulmonary infiltrates in an immunocompromised Peruvian man

The diagnostic considerations raised by immunocompromised patients with opportunistic infection continue to expand. When such patients harbor latent or persistent infection acquired in a tropical environment, the diagnostic challenge is even greater. The Infectious Disease Service at Yale-New Haven Hospital was asked to see a middle-aged man from Peru with known T-cell lymphoma who had recently completed a course of chemotherapy. He presented to the hospital with fever, petechial skin rash, pulmonary infiltrates, and neutropenia. Ultimately this case illustrated the necessity for careful evaluation of such patients, looking, in particular, for evidence of opportunistic parasitic infection.     

Real time bayesian estimation of the epidemic potential of emerging infectious diseases

Background

Fast changes in human demographics worldwide, coupled with increased mobility, and modified land uses make the threat of emerging infectious diseases increasingly important. Currently there is worldwide alert for H5N1 avian influenza becoming as transmissible in humans as seasonal influenza, and potentially causing a pandemic of unprecedented proportions. Here we show how epidemiological surveillance data for emerging infectious diseases can be interpreted in real time to assess changes in transmissibility with quantified uncertainty, and to perform running time predictions of new cases and guide logistics allocations.

Methodology/Principal Findings

We develop an extension of standard epidemiological models, appropriate for emerging infectious diseases, that describes the probabilistic progression of case numbers due to the concurrent effects of (incipient) human transmission and multiple introductions from a reservoir. The model is cast in terms of surveillance observables and immediately suggests a simple graphical estimation procedure for the effective reproductive number R (mean number of cases generated by an infectious individual) of standard epidemics. For emerging infectious diseases, which typically show large relative case number fluctuations over time, we develop a Bayesian scheme for real time estimation of the probability distribution of the effective reproduction number and show how to use such inferences to formulate significance tests on future epidemiological observations.

Conclusions/Significance

Violations of these significance tests define statistical anomalies that may signal changes in the epidemiology of emerging diseases and should trigger further field investigation. We apply the methodology to case data from World Health Organization reports to place bounds on the current transmissibility of H5N1 influenza in humans and establish a statistical basis for monitoring its evolution in real time.     

Effect of infectious factors on human and animal cytogenetic structures]

The analysis of blood leucocyte chromosomes has been carried out on 60 patients with different infectious diseases (influenza, measles, scarlet fever, and disentery), and on 47 patients immunized against measles, tick-born encephalitis, typhoid fever and brucellosis. The mutagenic influence of viruses on the genital cells of mice and on the human somatic cells in vitro was studied. Both viruses and bacteria appeared to be able to bring about different breaks in human and animal cells.