AlphaFold – A Personal Perspective on the Impact of Machine Learning

I outline how over my career as a protein scientist Machine Learning has impacted my area of science and one of my pastimes, chess, where there are some interesting parallels. In 1968, modelling of three-dimensional structures was initiated based on a known structure as a template, the problem of the pathway of protein folding was posed and bets were taken in the emerging field of Machine Learning on whether computers could outplay humans at chess. Half a century later, Machine Learning has progressed from using computational power combined with human knowledge in solving problems to playing chess without human knowledge being used, where it has produced novel strategies. Protein structures are being solved by Machine Learning based on human-derived knowledge but without templates. There is much promise that programs like AlphaFold based on Machine Learning will be powerful tools for designing entirely novel protein folds and new activities. But, will they produce novel ideas on protein folding pathways and provide new insights into the principles that govern folds?     

Occurrence and Abundance of Antibiotics and Resistance Genes in Rivers,Canal and near Drug Formulation Facilities – A Study in Pakistan

Antibiotic resistance (AR) is a global phenomenon that has severe epidemiological ramifications world-wide. It has been suggested that antibiotics that have been discharged into the natural aquatic environments after usage or manufacture can promote the occurrence of antibiotic resistance genes (ARG). These environmental ARGs could serve as a reservoir and be horizontally transferred to human-associated bacteria and thus contribute to AR proliferation. The aim of this study was to investigate the anthropogenic load of antibiotics in Northern Pakistan and study the occurrence of ARGs in selected samples from this region. 19 sampling sites were selected; including six rivers, one dam, one canal, one sewage drain and four drug formulation facilities. Our results show that five of the rivers have antibiotic levels comparable to surface water measurements in unpolluted sites in Europe and the US. However, high levels of antibiotics could be detected in the downstream river in close vicinity of the 10 million city Lahore, 1100, 1700 and 2700 ng L⁻¹ for oxytetracycline, trimethoprim, and sulfamethoxazole respectively. Highest detected levels were at one of the drug formulation facilities, with the measured levels of 1100, 4100, 6200, 7300, 8000, 27000, 28000 and 49000 ng L⁻¹ of erythromycin, lincomycin, ciprofloxacin, ofloxacin, levofloxacin, oxytetracycline, trimethoprim and sulfamethoxazole respectively. ARGs were also detected at the sites and the highest levels of ARGs detected, sulI and dfrA1, were directly associated with the antibiotics detected at the highest concentrations, sulfamethoxazole and trimethoprim. Highest levels of both antibiotics and ARGs were seen at a drug formulation facility, within an industrial estate with a low number of local residents and no hospitals in the vicinity, which indicates that the levels of ARGs at this site were associated with the environmental levels of antibiotics.     

VIS – A database on the distribution of fishes in inland and estuarine waters in Flanders,Belgium

The Research Institute for Nature and Forest (INBO) has been performing standardized fish stock assessments in Flanders, Belgium. This Flemish Fish Monitoring Network aims to assess fish populations in public waters at regular time intervals in both inland waters and estuaries. This monitoring was set up in support of the Water Framework Directive, the Habitat Directive, the Eel Regulation, the Red List of fishes, fish stock management, biodiversity research, and to assess the colonization and spreading of non-native fish species. The collected data are consolidated in the Fish Information System or VIS. From VIS, the occurrence data are now published at the INBO IPT as two datasets: ‘VIS - Fishes in inland waters in Flanders, Belgium’ and ‘VIS - Fishes in estuarine waters in Flanders, Belgium’. Together these datasets represent a complete overview of the distribution and abundance of fish species pertaining in Flanders from late 1992 to the end of 2012. This data paper discusses both datasets together, as both have a similar methodology and structure. The inland waters dataset contains over 350,000 fish observations, sampled between 1992 and 2012 from over 2,000 locations in inland rivers, streams, canals, and enclosed waters in Flanders. The dataset includes 64 fish species, as well as a number of non-target species (mainly crustaceans). The estuarine waters dataset contains over 44,000 fish observations, sampled between 1995 and 2012 from almost 50 locations in the estuaries of the rivers Yser and Scheldt (“Zeeschelde”), including two sampling sites in the Netherlands. The dataset includes 69 fish species and a number of non-target crustacean species. To foster broad and collaborative use, the data are dedicated to the public domain under a Creative Commons Zero waiver and reference the INBO norms for data use.     

A Perspective on the History and Evolution of an Oceans and Human Health “Metadiscipline” in the USA

We review recent history and evolution of Oceans and Human Health programs and related activities in the USA from a perspective within the Federal government. As a result of about a decade of support by the US Congress and through a few Federal agencies, notably the National Science Foundation, National Institute of Environmental Health Sciences, and National Ocean and Atmospheric Administration, robust Oceans and Human Health (OHH) research and application activities are now relatively widespread, although still small, in a number of agencies and academic institutions. OHH themes and issues have been incorporated into comprehensive federal ocean research plans and are reflected in the new National Ocean Policy enunciated by Executive Order 13547. In just a decade, OHH has matured into a recognized “metadiscipline,” with development of a small, but robust and diverse community of science and practice, incorporation into academic educational programs, regular participation in ocean and coastal science and public health societies, and active engagement with public health decision makers. In addition to substantial increases in scientific information, the OHH community has demonstrated ability to respond rapidly and effectively to emergency situations such as those associated with extreme weather events (e.g., hurricanes, floods) and human-caused disasters (e.g., the Deep Water Horizon oil spill). Among many other things, next steps include development and implementation of agency health strategies and provision of specific services, such as ecological forecasts to provide routine early warnings for ocean health threats and opportunities for prevention and mitigation of these risks.     

Cadmium induced bioaccumulation,histopathology, gene regulation in fish and its amelioration – A review

Different anthropogenic activities as well as natural sources contribute enormously towards various heavy metal contaminations in aquatic habitats. Cadmium (Cd) is one of most prevalent and toxic heavy metals with a long half life. Unlike terrestrial animals, exposure of Cd in fishes may happen not only through feeds but also from its habitat water. Bioaccumulation of Cd in fishes occurs in many tissues, but mainly in gill, liver, kidney, skin, and muscle. The concentrations of Cd in fish tissues depend upon the extent and duration of Cd exposure, species and age of fishes, dietary minerals and antioxidant concentrations, and habitat water quality. Specific histopathological observations in liver, kidney, and gill are useful to understand the effects of Cd, which could help to determine the ameliorating methods to be adopted. Exposure of Cd exerts several adverse effects on general growth and development, reproductive processes, osmoregulation, morphological and histological structures, stress tolerance, and endocrine system, mainly due to changes in biological functions induced by differential expressions of several genes related to oxidative stress, apoptosis, inflammation, immunosuppressions, genotoxicity, Cd chelation and carbohydrate metabolism. Chronic biomagnifications of Cd exceeding the permitted level may be harmful not only to the fishes itself but also to humans through food chains. Amelioration of such toxic heavy metal that has been categorized as a potent carcinogenic in humans is of utmost importance. Main modes of amelioration encompas reducing oxidative damages by promoting the antioxidative defenses, decreasing Cd absorption, increasing excretion through excretory system and improving the tolerance of fishes to Cd toxicity. Many amelioration measures such as use of minerals (for example, zinc, calcium, and iron), vitamins (vitamin C, A, and E), different herbs, probiotics and other agents (taurine, bentonite, chitosan, zeolite, and metallothionein) have been explored for their effective roles to reduce Cd bioaccumulation and toxicity symptoms in fishes. The present review discusses bioaccumulation of Cd, histopathological alterations, oxidative stress, synergism-antagonism, and gene regulation in different tissues, and its amelioration measures in fishes.     

Eutrophication of the Salt Valley Reservoirs, 1968–73 III. The macroinvertebrate community: Its development,composition, and change in response to eutrophication

The macroinvertebrate communities of four flood control reservoirs in eastern Nebraska, differing in age and degree of eutrophy were investigated from Ekman grab samples. Generally, the longer a reservoir had been influenced by eutrophication the larger the standing crop in it. Chironomids, ceratopogonids, fingernail clams, and Hexagenia were important at various stages of eutrophication with Chironomus predominating in the most eutrophic reservoirs. Tubifex decreased with eutrophication as did Sphaerium simili while Sphaerium declive maintained its abundance and sometimes increased.The chironomids Chironomus, Coelotanypus, and Procladius, fingernail clams, and Tubifex were early colonizers in the newest reservoir and developed a total standing crop as large the first summer as in subsequent ones. However, its composition became more diverse with time. In one reservoir sampled year-round, the standing crop was largest in late fall or early winter and smallest during summer. The most accurate information on macro-invertebrate standing crops in lakes and reservoirs comes from data collected on a year-round basis.     

How robust is the Australian Weed Risk Assessment protocol? A test using pine invasions in the Northern and Southern hemispheres

The Australian Weed Risk Assessment protocol (WRA) is often considered the standard approach for pre-border screening of new plant introductions. Here we assess its robustness against three key criteria: ability to discriminate success or failure of species at three stages of the invasion process (introduction, naturalisation and spread); sensitivity to taxonomic range and target region; and dependence on knowledge of invasive behaviour elsewhere. We address these issues by retrospectively testing the WRA using pine (Pinus) introductions to New Zealand and Great Britain. For both regions we calculated WRA scores for 115 species, and classified all species according to whether they had been introduced, which of these had naturalised, and the extent of their naturalised distribution (spread). Using regression models, we assessed whether WRA scores could predict success at each stage. We repeated this procedure using WRA scores calculated without information on species naturalisation behaviour elsewhere. In both regions, the WRA could discriminate among species in the same genus at the introduction and naturalisation stages, but not at the spread stage. The outcome at the naturalisation stage depended on prior knowledge of naturalisation behaviour elsewhere. Without this information the WRA may be unable to distinguish among closely related species, and should be used cautiously where data on invasive behaviour elsewhere is lacking. Human selection played a strong role in the invasion process both through introducing pine species likely to naturalise in New Zealand and Great Britain in the first instance, and subsequent use of many of these species for forestry in the target regions.     

Effects of creatine and its analog, β-guanidinopropionic acid, on the differentiation of and nucleoli in myoblasts

The effects of supplementation with creatine (Cr) and its analog, β-guanidinopropionic acid (β-GPA), on the differentiation of myoblasts and the numbers of nucleoli were studied in C2C12 cells. The cells were cultured in differentiation medium for 4 d. Then Cr (1 mM) or β-GPA (1 mM) was added to the cells, and the mixture was cultured for an additional 2 d. Although the number of myotubes was not different among the groups, myotube diameters and nuclear numbers in myotubes were increased by Cr and β-GPA treatment respectively. The expression of differentiation marker proteins, myogenin, and the myosine heavy chain, was increased in the β-GPA group. Supplementation with β-GPA also increased the percentage of p21 (inhibitor for cell cycle progression)-positive myoblasts. Supplementation with Cr inhibited the decrease in nucleoli numbers, whereas β-GPA increased nucleolar sizes in the myotubes. These results suggest that β-GPA supplementation stimulated the differentiation of myoblasts into multi-nucleated myotubes through induction of p21 expression.     

Shadows of the colonial past – diverging plant use in Northern Peru and Southern Ecuador

This paper examines the traditional use of medicinal plants in Northern Peru and Southern Ecuador, with special focus on the Departments of Piura, Lambayeque, La Libertad, Cajamarca, and San Martin, and in Loja province, with special focus on the development since the early colonial period. Northern Peru represents the locus of the old Central Andean "Health Axis." The roots of traditional healing practices in this region go as far back as the Cupisnique culture early in the first millennium BC. Northern Peru and Southern Ecuador share the same cultural context and flora but show striking differences in plant use and traditional knowledge. Two hundred fifteen plant species used for medicinal purposes in Ecuador and 510 plant species used for medicinal purposes in Peru were collected, identified,. and their vernacular names, traditional uses, and applications recorded. This number of species indicates that the healers, market vendors, and members of the public interviewed in Peru still have a very high knowledge of plants in their surroundings, which can be seen as a reflection of the knowledge of the population in general. In Ecuador much of the original plant knowledge has already been lost. In Peru, 433 (85%) were Dicotyledons, 46 (9%) Monocotyledons, 21 (4%) Pteridophytes, and 5 (1%) Gymnosperms. Three species of Giartina (Algae) and one species of the Lichen genus Siphula were used. The families best represented were Asteraceae with 69 species, Fabaceae (35), Lamiaceae (25), and Solanaceae (21). Euphorbiaceae had 12 species, and Poaceae and Apiaceae each accounted for 11 species. In Ecuador the families best represented were Asteraceae (32 species), Euphorbiaceae, Lamiaceae, and Solanaceae (11 species each), and Apiaceae, Fabaceae, Lycopodiaceae (9 species each). One hundred eighty-two (85%) of the species used were Dicotyledons, 20 Monocotyledons (9.3%), 12 ferns (5.5%), and one unidentified lichen was used. Most of the plants used (83%) were native to Peru and Ecuador. Fresh plants, often collected wild, were used in two thirds of all cases in Peru, but in almost 95% of the cases in Ecuador. The most common applications included the ingestion of herb decoctions or the application of plant material as poultices. Although about 50% of the plants in use in the colonial period have disappeared from the popular pharmacopoeia, the overall number of plant species used medicinally has increased in Northern Peru, while Southern Ecuador shows a decline of plant knowledge since colonial times.     

Comets and the formation of biochemical compounds on the primitive Earth – A review

Thirty years ago it was suggested that comets impacting on the primitive Earth may have represented a significant source of terrestrial volatiles, including some important precursors for prebiotic synthesis (Oró, 1961,Nature 190: 389). This possibility is strongly supported not only by models of the collisional history of the early Earth, but also by astronomical evidence that suggests that frequent collisions of comet-like bodies from the circumstellar disk around the star Pictoris are taking place. Although a significant fraction of the complex organic compounds that appear to be present in cometary nuclei were probably destroyed during impact, it is argued that cometary collisions with the primitive Earth represented an important source of both free-energy and volatiles, and may have created transient, gaseous environments in which prebiotic synthesis may have taken place.     

Environmental Variables Associated with Hantavirus Reservoirs and Other Small Rodent Species in Two National Parks in the Paraná Delta,Argentina: Implications for Disease Prevention

Hantavirus pulmonary syndrome (HPS) is a severe zoonotic disease caused by hantaviruses hosted in various rodents species. In Argentina, its transmission to humans has been associated to exposure during activities such as farming, recreation, and tourism which are carried out in wild and rural areas. The aim of this study was to analyze the macro- and micro-habitat use and spatio–temporal variation of small sylvan rodents in Pre Delta and Islas de Santa Fe national parks, located in an HPS-endemic area of Argentina. Rodent communities were studied at six sites: two islands, a riparian forest, an inland forest, a marsh, and the margins of a pond. A total of 453 individuals of five species were captured with a trapping effort of 9471 trap-nights. Maximum species richness was found at the marsh and the pond margin sites. Abundance of rodents was influenced by flooding events. Two hantavirus reservoirs, Oligoryzomys flavescens and Akodon azarae, were identified in the area. O. flavescens was captured in every habitat, but it was dominant in Islas de Santa Fe National Park where its abundance was strongly influenced by flooding. A. azarae was captured in every habitat except on the islands. A. azarae behaved as a generalist species at a micro-habitat scale in every habitat of Pre Delta National Park except for the marsh where it selected patches with low vegetation height. Based on these results, several disease prevention measures, including the use of rodent-proof containers for food, and keeping the grass short in the camp site, are proposed in order to reduce the risk to visitors and residents of contracting HPS.     

Phenotypic responses to light,water, and nutrient conditions in the allopolyploid Arabidopsis suecica and its parent species A. thaliana and A. arenosa: Does the allopolyploid outrange its parents?

Polyploid species possess more than two sets of chromosomes and may show high gene redundancy, hybrid vigor, and masking of deleterious alleles compared to their parent species. Following this, it is hypothesized that this makes them better at adapting to novel environments than their parent species, possibly due to phenotypic plasticity. The allopolyploid Arabidopsis suecica and its parent species A. arenosa and A. thaliana were chosen as a model system to investigate relationships between phenotypic plasticity, fitness, and genetic variation. Particularly, we test if A. suecica is more plastic, show higher genetic diversity, and/or have higher fitness than its parent species. Wild Norwegian populations of each species were analyzed for phenotypic responses to differences in availability of nutrient, water, and light, while genetic diversity was assessed through analysis of AFLP markers. Arabidopsis arenosa showed a higher level of phenotypic plasticity and higher levels of genetic diversity than the two other species, probably related to its outbreeding reproduction strategy. Furthermore, a general positive relationship between genetic diversity and phenotypic plasticity was found. Low genetic diversity was found in the inbreeding A. thaliana. Geographic spacing of populations might explain the clear genetic structure in A. arenosa, while the lack of structure in A. suecica could be due to coherent populations. Fitness measured as allocation of resources to reproduction, pointed toward A. arenosa having lower fitness under poor environmental conditions. Arabidopsis suecica, on the other hand, showed tendencies toward keeping up fitness under different environmental conditions.     

Discussing epigenetics in Southern California: A report from the International Symposium on Epigenetic Control and Cellular Plasticity,UCI, December 15–16, 2011

With the goal of discussing how epigenetic control and chromatin remodeling contribute to the various processes that lead to cellular plasticity and disease, this symposium marks the collaboration between the Institut National de la Santé et de la Recherche Médicale (INSERM) in France and the University of California, Irvine (UCI). Organized by Paolo Sassone-Corsi (UCI) and held at the Beckman Center of the National Academy of Sciences at the UCI campus December 15–16, 2011, this was the first of a series of international conferences on epigenetics dedicated to the scientific community in Southern California. The meeting also served as the official kick off for the newly formed Center for Epigenetics and Metabolism at the School of Medicine, UCI (http://cem.igb.uci.edu).     

Discussing epigenetics in Southern California: A report from the International Symposium on Epigenetic Control and Cellular Plasticity,UCI, December 15–16, 2011

With the goal of discussing how epigenetic control and chromatin remodeling contribute to the various processes that lead to cellular plasticity and disease, this symposium marks the collaboration between the Institut National de la Santé et de la Recherche Médicale (INSERM) in France and the University of California, Irvine (UCI). Organized by Paolo Sassone-Corsi (UCI) and held at the Beckman Center of the National Academy of Sciences at the UCI campus December 15–16, 2011, this was the first of a series of international conferences on epigenetics dedicated to the scientific community in Southern California. The meeting also served as the official kick off for the newly formed Center for Epigenetics and Metabolism at the School of Medicine, UCI (http://cem.igb.uci.edu).     

Preventing Introduction of Livestock Associated MRSA in a Pig Population – Benefits,Costs, and Knowledge Gaps from the Swedish Perspective

Antibiotic resistance is a growing concern in human, as well as in veterinary medicine. Part of the problem concerns how to respond to the risk presented by animal reservoirs of resistant bacteria with the potential of spreading to humans. One example is livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA). In countries where LA-MRSA is endemic in the pig population, people in contact with pigs have a higher risk of being colonised with LA-MRSA, and persons from this group are subjected to precautionary measures when visiting health care facilities. In the present study, it is assumed that, if LA-MRSA was introduced to the Swedish pig population, the prevalence in the risk groups would be the same as in Denmark or the Netherlands (two countries with low human prevalence that have implemented measures to detect, trace and isolate human LA-MRSA cases and, therefore, have comprehensive data with good coverage regarding prevalence of LA-MRSA), and that similar interventions would be taken in Swedish health care facilities. It is also assumed that the Swedish pig population is free of MRSA or that the prevalence is very low. We analyse if it would be efficient for Sweden to prevent its introduction by testing imported live breeding pigs. Given that quarantining and testing at import will prevent introduction to the pig population, the study shows that the preventive measures may indeed generate a societal net benefit. Benefits are estimated to be between € 870 720 and € 1 233 511, and costs to € 211 129. Still, due to gaps in knowledge, the results should be confirmed when more information become available.