Flowing through India and Bangladesh, the Ganges is the most sacred river in Hinduism. However, wastewater from nearby cities severely pollutes the river. The Ganges empties into the Bay of Bengal, in the Indian Ocean, and is therefore influenced by tides. Seasonal monsoons also affect the river.

To better understand the impact of tides and seasons on the River Ganges, Kar and colleagues conducted a comprehensive water quality analysis between 2014 and 2018. They focused specifically on a stretch of the river in West Bengal, India, located between Howrah Station — a major railway station near Kolkata — and Khardah, another city near Kolkata.

In 2014, after an extensive survey, the researchers selected five major outfalls where city wastewater flows into the Ganges. At each outfall, for the next four years, they monitored river water quality according to several different parameters, including measurements known as dissolved oxygen and biochemical oxygen demand, as well as concentrations of various heavy metals and fecal coliform level — an indicator of potential contamination by human feces.

The analysis, which included GIS mapping, showed that dissolved oxygen and biochemical oxygen demand, as well as levels of nitrate nitrogen and chloride, were significantly higher at each of the five sites prior to monsoon season than during monsoon season. Additionally, heavy metal and fecal coliform levels were strongly correlated with each other, and measurement of one could be used to predict the other. The researchers were also able to use their data to mathematically model the influence of tides on various water quality parameters at the five sites.

Overall, the analysis provides new insights into how outfall wastewater impacts water quality in this stretch of the Ganges, depending on seasonal and tidal conditions. This information could help inform new guidelines for safe usage of river water.

The authors add: “River Ganges is not only a symbol of faith and hope for millions of people but is also used for daily human usage and livestock management. A collaboration between Asutosh College, Jadavpur University, and Navajo Technical University investigated the influence of river flow, tidal dynamics, and seasons on distribution of pollutants entering the river from different discharge points (city outfalls) at selected river stretches to prepare river water usage guidelines.”

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In recent years, national and global initiatives have made increasing efforts to address the tremendous burden posed by major depressive disorder. However, treatment rates remain low. Analyses that combine results from studies on depression treatment from different regions can help identify opportunities for improvement. However, many such analyses do not adequately account for variations in study methods that make results from different studies difficult to compare.

To provide further clarity, Ferrari and colleagues conducted an updated analysis of 149 studies on treatment for major depressive disorder conducted in 84 countries between 2000 and 2021. Applying a statistical method known as Bayesian meta-regression analysis, they combined the studies to examine treatment rates around the world.

The findings of this meta-analysis suggest that treatment rates remain low worldwide, and it highlights disparities in treatment between countries with different resource levels. In particular, use of mental health services by people with major depressive disorder is estimated to be 33 percent in high-income countries and just eight percent in low and lower-middle income countries.

Rates of treatment considered to be minimally sufficient for treating major depressive disorder are lower, estimated at 23 percent for high-income countries and 3 percent in low and lower-middle income countries.

The authors note a lack of high-quality data on depression treatment for low and lower-middle income countries, mostly in Sub-Saharan Africa and South Asia; further research could attempt to address that gap and thereby improve the accuracy of the treatment rates reported in this study. Future research could also examine how to best improve treatment access in different regions.

Overall, the researchers say, their findings could help inform efforts by governments and policymakers to more effectively address depression treatment worldwide.

Ferrari adds, “Treatment coverage for major depressive disorder continues to be low globally, with many individuals failing to receive a level of care consistent with practice guideline recommendations. This highlights the need to reconsider the availability of appropriate care and facilitators of treatment as we respond to the large burden imposed by this disorder.”

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The authors evaluated global repositories of DNA sequencing data used to measure microbiome content and found that almost half of all publicly available samples come from subjects in the U.S., even though that country represents only 4.3 percent of the global population. These findings raise questions about whether advances in the field will be applicable to countries that have fewer resources and populations that don’t receive as much attention in the literature.

The “human microbiome” refers to the communities of microorganisms living on and in the human body — estimates suggest a person’s human cells are greatly outnumbered by the trillions of bacteria making up their microbiome, living everywhere from the small intestine to the surface of the eyeball.

Research shows that these microbes have extensive interactions with their human hosts and have wide-ranging effects, both positive and negative. Some gut microbes, for example, help break down food into nutrients that humans cannot naturally access, while others have been linked to conditions such as inflammatory bowel disease, stomach cancer, and diabetes. Accordingly, billions of dollars have been invested in researching these relationships since the early 2000s. To understand where this funding was being used, the Minnesota researchers inventoried more than 440,000 samples of human microbiome data shared in international repositories maintained by organizations such as the National Institutes of Health in the United States and Japan’s National Institute of Genetics.

“Interest in the human microbiome has been growing worldwide,” said Richard Abdill, the study’s lead author. “When we look at how the field is developing, who is being included, and where resources have been allocated, it is clear that our understanding of the ‘human’ microbiome does not include most humans. Our study is a step towards quantifying this disparity.”

There are many reasons for these disparities, such as economic and political factors that impact scientific research, and logistical difficulties with performing research in countries with less infrastructure. However, the microbiome is in turn influenced by factors such as genetics, geography, diet, and lifestyle, making it important to study many populations to find links to human health. Because of this, the authors maintain that the exclusion of the developing world from microbiome research threatens to create a situation in which future microbiome-based medical treatments may only be effective for people in some countries or populations.

Of the samples for which a country of origin could be determined, the researchers found more than 71 percent came from Europe and North America, almost five times as many as would be expected given their population. Central and Southern Asia was the most underrepresented region: Though more than 2 billion people live in countries such as India, Pakistan, and Bangladesh, only 13,620 microbiome samples were available from that region, or 1.5 percent of samples from almost 26 percent of the world’s population. No samples at all were found from countries such as Algeria, Yemen, Afghanistan, and Kazakhstan.

Blekhman adds, “Interest in the human microbiome has been growing quickly, but there are conspicuous gaps in where that interest is being directed. Our study investigated all publicly available human microbiome samples — almost half a million samples — to quantify these gaps. We found that our understanding of the ‘human’ microbiome leaves out a lot of the humans.”

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It is precisely here that the interdisciplinary project “GreenToxiConomy,” which is part of the scientific alliance Bioeconomy Science Center (BioSC), comes into play. The objective was to examine bio-based substances and innovative technologies with a view to their toxic impact on the environment at an early stage in product development and to incorporate the resulting findings into product design. Project partners from Aachen, Jülich and Düsseldorf provided two of their bio-based product candidates for the analyses: microgel containers for crop protection agents and biosurfactants.

The wash-active biosurfactants for use in shampoos and detergents at BioSC are based on the synthesis abilities of the Pseudomonas putida bacterium and the Ustilago maydis fungus, respectively, rather than on crude oil. The microgel technology allows for the controlled delivery of crop protection agents because the containers ensure that the active ingredients still adhere to the plants in the event of rain.

Dr. Sarah Johann, the lead author for the study and the head of a working group in the department of evolutionary ecology and environmental toxicology at the Institute for Ecology, Evolution and Diversity at Goethe University Frankfurt, explains: “For the analysis of novel substances and technologies we have selected a broad range of concentration to be able to adequately estimate potential hazards for humans and the environment. We wanted to examine whether the bio-based surfactants were more environmentally friendly than conventional chemical surfactants. In addition, we investigated whether the microgel containers per se induce any toxicity.”

To ensure the ecotoxicological evaluation was as precise as possible, the project team combined two elements in the determination of the toxicity: computer-aided prognoses (in silico) and experiments in the laboratory (in vitro and in vivo). The computer models work with the toxicity data of known chemicals, whose structure they compared with the structure of the new bio-based substances to forecast the toxicity. The experiments were conducted on aquatic and terrestrial organisms that represent specific organism groups, among them earthworms, springtails, water fleas and zebrafish embryos at a very early stage.

The result: both biosurfactants and microgels are highly promising candidates for use in a future bioeconomy whose products must be sustainably manufactured while not causing any environmental damage or harm to humans both during and after their utilisation. “We can only make statements within certain limits, however, as the transfer of laboratory results to the reality in the open field or in other applications is complicated,” says Johann. More research is necessary for a holistic assessment of the risk potential, which is why follow-up projects are planned.

Prof. Henner Hollert, head of the evolutionary ecology and environmental toxicology department at Goethe University Frankfurt, underlines the significance of the close interdisciplinary collaboration on “GreenToxiConomy.” In the project biotechnologists and engineers jointly designed a new product, and this was evaluated during the development stages by eco-toxicologists from Goethe University together with a team at RWTH Aachen headed by Prof. Dr. Martina Roß-Nickoll. “This continuous process is the major strength of the project.” Although it is only a first step towards a bioeconomy that is safe in eco-toxicological terms, for Hollert it is already clear that eco-toxicology and green toxicology will play a key role in the plans being drawn up by the EU. “Whenever it is a question of future bio-based product development and product design, we have to clarify the consequences for humans and the environment at an early stage. In this respect our approach can provide valuable results.”

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Many of the craters are clustered in groups and are aligned along rays. Furthermore, several craters are elliptical, allowing the reconstruction of the incoming paths of the impactors. The reconstructed trajectories have a radial pattern.

“The trajectories indicate a single source and show that the craters were formed by ejected blocks from a large primary crater,” said project leader Thomas Kenkmann, professor of geology at the University of Freiburg, Germany. “Secondary craters around larger craters are well known from other planets and moons but have never been found on Earth,”

The team calculated the ballistic trajectories and used mathematical simulations to model the formation of the craters. All of the craters found so far are located 150-200 km from the presumed primary crater and were formed by blocks that were 4-8-m in size that struck the Earth at speeds of 700-1000 m/s. The team estimate that the source crater is about 50-65 km in diameter and should be deeply buried under younger sediments in the northern Denver basin near the Wyoming-Nebraska border.

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Journal Reference:

1. Thomas Kenkmann, Louis Müller, Allan Fraser, Doug Cook, Kent Sundell, Auriol S.P. Rae. Secondary cratering on Earth: The Wyoming impact crater field. GSA Bulletin, 2022; DOI: 10.1130/B36196.1

The research was conducted primarily in the laboratory of Sarkis Mazmanian, Luis B. and Nelly Soux Professor of Microbiology and affiliated faculty member with the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. A paper describing the study appears on February 14 in the journal Nature.

Decades of research have shown that the communities of bacteria that inhabit the intestines of animals (the microbiome) influence the immune system and metabolism; studies in the last few years have linked the microbiome to brain function and mood. People with certain neurological conditions have distinctly different gut bacteria communities. Further, studies in mice have shown that manipulating these communities can alter neurodevelopmental and neurodegenerative states, either ameliorating or exacerbating symptoms.

“It’s been really difficult to show causation between something that’s happening in the gut and the brain, rather than just associations between the disease states and the presence or absence of certain microbes,” says Brittany Needham, first author of the new study and a postdoctoral scholar in the Mazmanian lab. “We were interested in trying to understand the molecular messages that are going between the gut and the brain, and how these signals may lead to changes in behavior.”

This study focused on a bacterial metabolite (a by-product of microbes) called 4-ethylphenyl sulfate, or 4EPS. Initially produced by microbes in the intestines, 4EPS is then absorbed into the bloodstream and circulates throughout the body in both humans and mice. In 2013, the Mazmanian lab showed that this particular molecule was present in higher levels in mice with altered neurological development, specifically, a mouse model of autism and schizophrenia. Though other aspects of the altered microbiome differed from the healthy microbiome, 4EPS levels were by far the most different. Additionally, in a screen of human blood samples from 231 individuals, 4EPS levels were about seven times higher in children on the autism spectrum than in neurotypical children.

In this work, the team focused on the effects of 4EPS on mouse models of anxiety. While anxiety disorders in humans are complex, animal models provide a way to study the precise changes in the brain and body that lead to anxious behaviors. “Anxiety” in mice is measured by their willingness to explore or hide in a new space as well as the time spent in a risky environment. Bold mice will explore a new space, sniffing around, but anxious mice will hide, as if facing a predator, instead of exploring.

The study compared two groups of laboratory mice: one group was colonized with a pair of bacteria that were genetically engineered to produce 4EPS; the control group of mice were colonized with bacteria that were identical except lacked the ability to produce 4EPS. Then, the mice were introduced to a new arena, and researchers measured each mouse’s behavior.

The mice with 4EPS spent much less time exploring the area and more time hiding as compared to their non-4EPS counterparts, indicating higher levels of anxiety. Brain scans of the 4EPS mice also showed that some of the brain regions associated with fear and anxiety were more activated in addition to overall changes in brain activity and functional connectivity.

Looking closer at brain cells within these altered regions, the team found that particular cells called oligodendrocytes were altered. These cells are important in part because they produce a protein called myelin, which acts as a protective coating around neurons and nerve fibers called axons, like insulation around an electrical wire. The team found that in the presence of 4EPS, oligodendrocytes are less mature and consequently produce less myelin, leading to thinner insulation around axons.

However, when the 4EPS mice were treated with a drug known to increase myelin production in oligodendrocytes, the drug was able to overpower the negative effects of 4EPS — the mice regained normal myelin production, and the anxious behaviors were reduced.

In a related study appearing simultaneously in the journal Nature Medicine, Needham showed that treating mice with an oral drug to soak up and remove 4EPS from their systems led to reductions in anxious behaviors. This result enabled a small clinical study that also gave humans the drug in an open-label trial (no placebo or control group). Sequestering 4EPS in the human gut led to reduced levels of 4EPS in the blood and urine, and many of the 26 study participants displayed overall decreased levels of anxiety.

“It’s an exciting proof-of-concept finding that a specific microbial metabolite alters the activity of brain cells and complex behaviors in mice, but how this is happening remains unknown,” says Mazmanian. “The basic framework for brain function includes integration of sensory and molecular cues from the periphery and even the environment. What we show here is similar in principle but with the discovery that the neuroactive molecule is of microbial origin. I believe this work has implications for human anxiety or other mood conditions.”

The next steps for the work are to examine the mechanisms through which 4EPS affects oligodendrocytes — which proteins it may be interacting with, whether 4EPS is affecting changes directly in the brain, or if it is affecting another part of the body and those effects are making their way up to the brain. Also, it will be critical to show that the human data have an effect in a well-powered and controlled clinical trial, which is now underway.

In addition to Needham and Mazmanian, Caltech co-authors are former research technician Mark Adame; research technician Joseph Boktor; former postdoctoral scholar Wei-Li Wu (now of National Cheng Kung University in Taiwan); postdoctoral scholar Claire Rabut; EM scientist Mark Ladinsky; lecturer in chemistry Son-Jong Hwang; graduate student Jessica Griffiths; Pamela Bjorkman, David Baltimore Professor of Biology and Bioengineering, Merkin Institute Professor, and executive officer for biology and biological engineering; and Mikhail Shapiro, professor of chemical engineering and Howard Hughes Medical Institute Investigator.

Additional co-authors are Masanori Funabashi of Stanford University and Daiichi Sankyo RD Novare Co.; Zhuo Wang, Yumei Guo, and Daniel Holschneider of USC; Jillian Haney and Daniel Geschwind of UCLA; Qiyun Zhu of UC San Diego and Arizona State University; Rob Knight of UC San Diego; and Michael Fischbach of Stanford University.

Funding was provided by the Center for Environmental Microbial Interactions, the National Science Foundation, the Human Frontier Science Program, the National Institutes of Health, the Ministry of Science and Technology in Taiwan, the Heritage Medical Research Institute, and Lynda and Blaine Fetter. Sarkis Mazmanian is co-founder of Axial Therapeutics, which conducted the clinical trial.