Question 7: The First Units of Life Were Not Simple Cells

Five common assumptions about the first cells are challenged by the pre-biotic ecology model and are replaced by the following propositions: firstly, early cells were more complex, more varied and had a greater diversity of constituents than modern cells; secondly, the complexity of a cell is not related to the number of genes it contains, indeed, modern bacteria are as complex as eukaryotes; thirdly, the unit of early life was an ‘ecosystem’ rather than a ‘cell’; fourthly, the early cell needed no genes at all; fifthly, early life depended on non-covalent associations and on catalysts that were not confined to specific reactions. We present here the outlines of a theory that connects findings about modern bacteria with speculations about their origins. Presented at the International School of Complexity – 4th Course: Basic Questions on the Origins of Life; “Ettore Majorana” Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006.     

An Open Question on the Origin of Life: The First Forms of Metabolism

The general framework of the origin of life on Earth is outlined, emphasizing that the so‐called prebiotic ‘RNA world’ is as yet on shaky scientific ground, and that one should any way ask the question of the structure of the first protocellular compartments capable of the initial forms of metabolism. This question is the basis of the research project on the minimal cells, containing the minimal and sufficient complexity capable of leading to life. Such research is briefly summarized, highlighting experiments with liposome‐based semisynthetic cells which are capable of ribosomal protein synthesis with a very minimal number of enzymes. The most recent finding in this area of research is the unexpected observation that the formation and closure of liposomes in situ acts as an attractor for the solute molecules in solution, bringing about a very high local concentration in some of the liposomes. It is argued that this spontaneous overcrowding, which permits reactions which are not possible in the original dilute solution, might be the origin of cellular metabolism for the origin of life on Earth.     

Avian Response to Bottomland Hardwood Reforestation: The First 10 Years

Bottomland hardwood forests were planted on agricultural fields in Mississippi and Louisiana predominantly using either Quercus species (oaks) or Populus deltoides (eastern cottonwood). We assessed avian colonization of these reforested sites between 2 and 10 years after planting. Rapid vertical growth of cottonwoods (circa 2–3 m/year) resulted in sites with forest structure that supported greater species richness of breeding birds, increased Shannon diversity indices, and supported greater territory densities than on sites planted with slower‐growing oak species. Grassland birds (Spiza americana[Dickcissel] and Sturnella magna[Eastern Meadowlark]) were indicative of species breeding on oak‐dominated reforestation no more than 10 years old. Agelaius phoeniceus (Red‐winged Blackbird) and Colinus virginianus (Northern Bobwhite) characterized cottonwood reforestation no more than 4 years old, whereas 14 species of shrub‐scrub birds (e.g., Passerina cyanea[Indigo Bunting]) and early‐successional forest birds (e.g., Vireo gilvus[Warbling vireo]) typified cottonwood reforestation 5 to 9 years after planting. Rates of daily nest survival did not differ between reforestation strategies. Nest parasitism increased markedly in older cottonwood stands but was overwhelmed by predation as a cause of nest failure. Based on Partners in Flight prioritization scores and territory densities, the value of cottonwood reforestation for avian conservation was significantly greater than that of oak reforestation during their first 10 years. Because of benefits conferred on breeding birds, we recommend reforestation of bottomland hardwoods should include a high proportion of fast‐growing early successional species such as cottonwood.     

Chagas Disease Vector Control in a Hyperendemic Setting: The First 11 Years of Intervention in Cochabamba,Bolivia

Background

Chagas disease has historically been hyperendemic in the Bolivian Department of Cochabamba. In the early 2000s, an extensive vector control program was implemented; 1.34 million dwelling inspections were conducted to ascertain infestation (2000–2001/2003–2011), with blanket insecticide spraying in 2003–2005 and subsequent survey-spraying cycles targeting residual infestation foci. Here, we assess the effects of this program on dwelling infestation rates (DIRs).

Methodology/Principal Findings

Program records were used to calculate annual, municipality-level aggregate DIRs (39 municipalities); very high values in 2000–2001 (median: 0.77–0.69) dropped to ∼0.03 from 2004 on. A linear mixed model (with municipality as a random factor) suggested that infestation odds decreased, on average, by ∼28% (95% confidence interval [CI₉₅] 6–44%) with each 10-fold increase in control effort. A second, better-fitting mixed model including year as an ordinal predictor disclosed large DIR reductions in 2001–2003 (odds ratio [OR] 0.11, CI₉₅ 0.06–0.19) and 2003–2004 (OR 0.22, CI₉₅ 0.14–0.34). Except for a moderate decrease in 2005–2006, no significant changes were detected afterwards. In both models, municipality-level DIRs correlated positively with previous-year DIRs and with the extent of municipal territory originally covered by montane dry forests.

Conclusions/Significance

Insecticide-spraying campaigns had very strong, long-lasting effects on DIRs in Cochabamba. However, post-intervention surveys consistently detected infestation in ∼3% of dwellings, underscoring the need for continuous surveillance; higher DIRs were recorded in the capital city and, more generally, in municipalities dominated by montane dry forest – an eco-region where wild Triatoma infestans are widespread. Traditional strategies combining insecticide spraying and longitudinal surveillance are thus confirmed as very effective means for area-wide Chagas disease vector control; they will be particularly beneficial in highly-endemic settings, but should also be implemented or maintained in other parts of Latin America where domestic infestation by triatomines is still commonplace.     

Patterns,Predictors, and Outcomes of Falls Trajectories in Older Adults: The MOBILIZE Boston Study with 5 Years of Follow-Up

Background

Falls may occur as unpredictable events or in patterns indicative of potentially modifiable risks and predictive of adverse outcomes. Knowing the patterns, risks, and outcomes of falls trajectories may help clinicians plan appropriate preventive measures. We hypothesized that clinically distinct trajectories of falls progression, baseline predictors and their coincident clinical outcomes could be identified.

Methods

We studied 765 community-dwelling participants in the MOBILIZE Boston Study, who were aged 70 and older and followed prospectively for falls over 5 years. Baseline demographic and clinical data were collected by questionnaire and a comprehensive clinic examination. Falls, injuries, and hospitalizations were recorded prospectively on daily calendars. Group-Based Trajectory Modeling (GBTM) was used to identify trajectories.

Results

We identified 4 distinct trajectories: No Falls (30.1%), Cluster Falls (46.1%), Increasing Falls (5.8%) and Chronic Recurring Falls (18.0%). Predictors of Cluster Falls were faster gait speed (OR 1.69 (95CI, 1.50–2.56)) and fall in the past year (OR 3.52 (95CI, 2.16–6.34)). Predictors of Increasing Falls were Diabetes Mellitus (OR 4.3 (95CI, 1.4–13.3)) and Cognitive Impairment (OR 2.82 (95CI, 1.34–5.82)). Predictors of Chronic Recurring Falls were multi-morbidity (OR 2.24 (95CI, 1.60–3.16)) and fall in the past year (OR 3.82 (95CI, 2.34–6.23)). Symptoms of depression were predictive of all falls trajectories. In the Chronic Recurring Falls trajectory group the incidence rate of Hospital visits was 121 (95% CI 63–169) per 1,000 person-years; Injurious falls 172 (95% CI 111–237) per 1,000 person-years and Fractures 41 (95% CI 9–78) per 1,000 person-years.

Conclusions

Falls may occur in clusters over discrete intervals in time, or as chronically increasing or recurring events that have a relatively greater risk of adverse outcomes. Patients with multiple falls, multimorbidity, and depressive symptoms should be targeted for preventive measures.     

A Brief History of the Biological Stain Commission: its Founders,its Mission and the First 75 Years

The need for batch-to-batch consistency in available dyes and stains used for biological purposes posed a considerable problem for United States scientists following World War I. Prior to that time, most of the acceptable stains in this country were of German origin. In an attempt to standardize the performance of biological stains and dyes, the Society of American Bacteriologists in 1922 appointed Dr. Harold Conn to form the Committee on the Standardization of Biological Stains. To assist him, Dr. Conn recruited scientists from several major professional scientific societies. Mr. Holland Will, a Rochester, NY, vendor of stains, was also instrumental in the Committee's success. This article traces the origin, mission and accomplishments of the product of that Committee, the Biological Stain Commission, through the past 75 years, and focuses on some of the major events that influenced and shaped its development.     

A Brief History of the Biological Stain Commission: its Founders, its Mission and the First 75 Years

The need for batch-to-batch consistency in available dyes and stains used for biological purposes posed a considerable problem for United States scientists following World War I. Prior to that time, most of the acceptable stains in this country were of German origin. In an attempt to standardize the performance of biological stains and dyes, the Society of American Bacteriologists in 1922 appointed Dr. Harold Conn to form the Committee on the Standardization of Biological Stains. To assist him, Dr. Conn recruited scientists from several major professional scientific societies. Mr. Holland Will, a Rochester, NY, vendor of stains, was also instrumental in the Committee's success. This article traces the origin, mission and accomplishments of the product of that Committee, the Biological Stain Commission, through the past 75 years, and focuses on some of the major events that influenced and shaped its development.     

Obcells as Proto-Organisms: Membrane Heredity, Lithophosphorylation, and the Origins of the Genetic Code, the First Cells, and Photosynthesis

I attempt to sketch a unified picture of the origin of living organisms in their genetic, bioenergetic, and structural aspects. Only selection at a higher level than for individual selfish genes could power the cooperative macromolecular coevolution required for evolving the genetic code. The protein synthesis machinery is too complex to have evolved before membranes. Therefore a symbiosis of membranes, replicators, and catalysts probably mediated the origin of the code and the transition from a nucleic acid world of independent molecular replicators to a nucleic acid/protein/lipid world of reproducing organisms. Membranes initially functioned as supramolecular structures to which different replicators attached and were selected as a higher-level reproductive unit: the proto-organism. I discuss the roles of stereochemistry, gene divergence, codon capture, and selection in the code's origin. I argue that proteins were primarily structural not enzymatic and that the first biological membranes consisted of amphipathic peptidyl-tRNAs and prebiotic mixed lipids. The peptidyl-tRNAs functioned as genetically-specified lipid analogues with hydrophobic tails (ancestral signal peptides) and hydrophilic polynucleotide heads. Protoribosomes arose from two cooperating RNAs: peptidyl transferase (large subunit) and mRNA-binder (small subunit). Early proteins had a second key role: coupling energy flow to the phosphorylation of gene and peptide precursors, probably by lithophosphorylation by membrane-anchored kinases scavenging geothermal polyphosphate stocks. These key evolutionary steps probably occurred on the outer surface of an `inside out-cell' or obcell, which evolved an unambiguous hydrophobic code with four prebiotic amino acids and proline, and initiation by isoleucine anticodon CAU; early proteins and nucleozymes were all membrane-attached. To improve replication, translation, and lithophosphorylation, hydrophilic substrate-binding and catalytic domains were later added to signal peptides, yielding a ten-acid doublet code. A primitive proto-ecology of molecular scavenging, parasitism, and predation evolved among obcells. I propose a new theory for the origin of the first cell: fusion of two cup-shaped obcells, or hemicells, to make a protocell with double envelope, internal genome and ribosomes, protocytosol, and periplasm. Only then did water-soluble enzymes, amino acid biosynthesis, and intermediary metabolism evolve in a concentrated autocatalytic internal cytosolic soup, causing 12 new amino acid assignments, termination, and rapid freezing of the 22-acid code. Anticodons were recruited sequentially: GNN, CNN, INN, and *UNN. CO₂ fixation, photoreduction, and lipid synthesis probably evolved in the protocell before photophosphorylation. Signal recognition particles, chaperones, compartmented proteases, and peptidoglycan arose prior to the last common ancestor of life, a complex autotrophic, anaerobic green bacterium. Received: 19 February 2001 / Accepted: 9 April 2001     

Bacillus anthracis Inosine 5'-Monophosphate Dehydrogenase in Action: The First Bacterial Series of Structures of Phosphate Ion-, Substrate-, and Product-Bound Complexes

Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the first unique step of the GMP branch of the purine nucleotide biosynthetic pathway. This enzyme is found in organisms of all three kingdoms. IMPDH inhibitors have broad clinical applications in cancer treatment, as antiviral drugs and as immunosuppressants, and have also displayed antibiotic activity. We have determined three crystal structures of Bacillus anthracis IMPDH, in a phosphate ion-bound (termed "apo") form and in complex with its substrate, inosine 5'-monophosphate (IMP), and product, xanthosine 5'-monophosphate (XMP). This is the first example of a bacterial IMPDH in more than one state from the same organism. Furthermore, for the first time for a prokaryotic enzyme, the entire active site flap, containing the conserved Arg-Tyr dyad, is clearly visible in the structure of the apoenzyme. Kinetic parameters for the enzymatic reaction were also determined, and the inhibitory effect of XMP and mycophenolic acid (MPA) has been studied. In addition, the inhibitory potential of two known Cryptosporidium parvum IMPDH inhibitors was examined for the B. anthracis enzyme and compared with those of three bacterial IMPDHs from Campylobacter jejuni, Clostridium perfringens, and Vibrio cholerae. The structures contribute to the characterization of the active site and design of inhibitors that specifically target B. anthracis and other microbial IMPDH enzymes.     

The 'home' in homeland: gender,national space,and Inkatha's politics of ethnicity

In South Africa, a country in which the manipulation of ethnicity was at the heart of the government's attempts to establish control over the majority African population, ethnic mobilization during the liberation struggle was singularly unsuccessful. The one exception was Chief Mangosuthu Buthelezi's controversial Inkatha movement. This article suggests that one of the reasons for Inkatha's successes was the astute way in which the organization and, in particular, Buthelezi played on gendered notions of 'home' and 'homeland'. Historically, apartheid constructed notions of home and space differently for women and men and Inkatha was able to draw upon and manipulate these differences to produce a powerfully felt response. Thus, for men, many of them migrant workers in South Africa's cities, the notion of 'home' implied a return to patriarchal values and male domestic control in a historically constituted 'homeland'; for women, Buthelezi emphasized the new 'modern' opportunities opened up by the KwaZulu homeland, and the importance of their 'God-given' gifts of motherhood.     

The Case of Heinrich Wilhelm Poll (1877–1939): A German-Jewish Geneticist, Eugenicist, Twin Researcher, and Victim of the Nazis

This paper uses a reconstruction of the life and career of Heinrich Poll as a window into developments and professional relationships in the biological sciences in Germany in the period from the beginning of the twentieth century to the Nazi seizure of power in 1933. Poll’s intellectual work involved an early transition from morphometric physical anthropology to comparative evolutionary studies, and also found expression in twin research – a field in which he was an acknowledged early pioneer. His advocacy of eugenics led to participation in state-sponsored committees convened to advise on social policy, one of which debated sterilisation and made recommendations that led eventually to the establishment of the notorious Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics. However, his status as a prominent geneticist and, in particular, as a eugenicist had an ironic and ultimately tragic dimension. Heinrich Poll was of Jewish birth, and this resulted in his career being destroyed by an application of the population policies he had helped put in place.     

The American Society for Neurochemistry (ASN): Antecedents, Founding, and Early Years

Events leading to and the influences on the founding of the American Society for Neurochemistry are recounted, with emphasis on early activities of neurochemists in the United States, as well as the international activities, that led to the founding of both the International and American societies (in 1965 and 1969, respectively). The founding of the American Society for Neurochemistry in the period 1968-1969 and its first annual meeting in 1970 are described, together with significant developments during the early years of the Society.     

The Mitochondrial Genome of a Deep-Sea Bamboo Coral (Cnidaria,Anthozoa, Octocorallia,Isididae): Genome Structure and Putative Origins of Replication Are Not Conserved Among Octocorals

Octocoral mitochondrial (mt) DNA is subject to an exceptionally low rate of substitution, and it has been suggested that mt genome content and structure are conserved across the subclass, an observation that has been supported for most octocorallian families by phylogenetic analyses using PCR products spanning gene boundaries. However, failure to recover amplification products spanning the nad4L-msh1 gene junction in species from the family Isididae (bamboo corals) prompted us to sequence the complete mt genome of a deep-sea bamboo coral (undescribed species). Compared to the "typical" octocoral mt genome, which has 12 genes transcribed on one strand and 5 genes on the opposite (cox2, atp8, atp6, cox3, trnM), in the bamboo coral genome a contiguous string of 5 genes (msh1, rnl, nad2, nad5, nad4) has undergone an inversion, likely in a single event. Analyses of strand-specific compositional asymmetry suggest that (i) the light-strand origin of replication was also inverted and is adjacent to nad4, and (ii) the orientation of the heavy-strand origin of replication (OriH) has reversed relative to that of previously known octocoral mt genomes. Comparative analyses suggest that intramitochondrial recombination and errors in replication at OriH may be responsible for changes in gene order in octocorals and hexacorals, respectively. Using primers flanking the regions at either end of the inverted set of five genes, we examined closely related taxa and determined that the novel gene order is restricted to the deep-sea subfamily Keratoisidinae; however, we found no evidence for strand-specific mutational biases that may influence phylogenetic analyses that include this subfamily of bamboo corals.     

Discovery of ML326: The first sub-micromolar,selective M5 PAM

This Letter describes the further chemical optimization of the M₅ PAM MLPCN probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172. An HTS campaign identified several weak M₅ PAMs (M₅ EC₅₀ >10 μM) with a structurally related isatin core that possessed a southern phenethyl ether linkage. While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M₅ PAM, ML326 (VU0467903), (human and rat M₅ EC₅₀s of 409 nM and 500 nM, respectively) with excellent mAChR selectivity (M₁–M₄ EC₅₀s >30 μM) and a robust 20-fold leftward shift of the ACh CRC.     

The Effects of Peatland Restoration on Water‐Table Depth,Elemental Concentrations,and Vegetation: 10 Years of Changes

We studied the effects of restoration on water‐table depth (WTD), element concentrations of peat and vegetation composition of peatlands drained for forestry in southern Finland. The restoration aimed to return the trajectory of vegetation succession toward that of undisturbed systems through the blockage of ditches and the removal of trees. Permanent plots established on a bog and a fen were sampled 1 year before, and 1, 2, 3, and 10 years after the restoration. The restoration resulted in a long‐term rise of the water‐table in both peatlands. Ten years after restoration, the mineral element concentrations (Ca, K, Mg, Mn, and P) of peat corresponded to those reported from comparable pristine peatlands. In particular, the increase of K and Mn concentrations at both sites suggests the recovery of ecosystem functionality in terms of nutrient cycling between peat and plants. The restoration resulted in the succession of plant communities toward the targeted peatland vegetation of wetter condition at both sites. This was evident from the decreased abundance of species benefiting from drainage and the corresponding increase of peatland species. However, many species typical of pristine peatlands were missing 10 years after restoration. We conclude that the restoration led to a reversal of the effects of drainage in vegetation and studied habitat conditions. However, due to the slow recovery of peatland ecosystems and the possibility that certain failures in the restoration measures may become apparent only after extended time periods, long‐term monitoring is needed to determine whether the goals of restoration will be met.     

The soapberry bug,Jadera haematoloma (Insecta,Hemiptera, Rhopalidae): First Asian record,with?a?review of bionomics

The soapberry bug, Jadera haematoloma (Herrich-Schäffer, 1847) (Insecta: Hemiptera: Heteroptera: Rhopalidae: Serinethinae), a species native in tropical and subtropical regions of the New World and accidentally introduced to Hawaii, is reported for the first time from Asia (Taiwan). This record represents the first occurrence of the species in Asia. Stable populations composed of hundreds of specimens were found in seven localities of Kaohsiung City and one locality in Tainan City, and a single specimen was observed in Chiayi County. Aggregating adults and larvae fed in large numbers on the sapindacean plants Cardiospermum halicacabum L. and Koelreuteria elegans (Seem.) A. C. Smith ssp. formosana (Hayata) F. G. Meyer. Diagnostic characters of adults and larvae of Jadera haematoloma are discussed. A review of its bionomics and a bibliography are provided. Initial observations on the populations in southern Taiwan are presented. The species is potentially invasive, and further extension of its range is anticipated in Southeast Asia.     

Nocardia beijingensis,is a Pathogenic Bacterium to Humans: The First Infectious Cases in Thailand and Japan

Nocardia beijingensis, a recently established new species, is an isolate from soil in China. During our taxonomic studies on 450 nocardial clinical isolates in Thailand and Japan, 17 strains from Thailand and 1 strain from Japan were found to have a similar physiological characteristic to those of N. beijingensis, such as a drug susceptibility pattern to three antimicrobial agents. Our phylogenetic studies on these 18 strains by 16S rRNA gene sequence analysis confirmed that these strains belong to N. beijingensis species. Phylogenetically, these newly isolated N. beijingensis strains were found to be classified into two distinct clades: one is a Japanese clade and other is a Chinese clade, including a reference strain and 17 Thai strains. This is the first report of human infection due to N. beijingensis strains, and we propose that the bacterium be categorized as an opportunistic infectious group regardless of its original isolation from soil.