These detailed findings include 3D views of the structure and position of the virus’ envelope “spike” proteins (the Env protein, used when the virus binds with cells) in the context of the full virus. Normally, researchers view the protein particles separated from the virus or expressed as engineered or purified proteins. In another key development, the scientists shed new light on the glycan shields — the sugars on the proteins that can hide it from the body’s immune system.

“We’re looking at the whole virus particle and how this protein on the surface relates to the rest of the virus,” said lead author Kelly Lee, associate professor of medicinal chemistry in the UW School of Pharmacy. “And by looking at the intact virus structure, we can see how the different facets of this ‘face of the virus’ are being displayed and how they would be recognized by or hidden from the immune system.”

This intact view of the virus also allowed the scientists to gain new insights into positioning of the envelope spike protein on the surface relative to the internal protein structure, called the Gag lattice.

“This finding overturns previous models of how the parts of the viruses are assembled and helps to focus our attention on where the docking interaction of these two proteins is likely to be,” Lee said. “This interaction needs to be resolved in more detail, but at least the current work gives us the correct architectural model for the virus assembly.”

It was this particular finding that led to the title of the paper — “Cryo-ET of Env on intact HIV virions reveals structural variations and positioning on the Gag lattice” — published Feb. 4 in the journal Cell. Another finding that had not been previously observed, the scientists pointed out, is that the “stalk” supporting the envelope proteins is flexible and can tilt, presenting both opportunity and challenges to the immune system’s neutralizing antibodies that protect cells from infection.

“Structural biology has driven HIV vaccine design, so as we get a better and better picture of what it is we’re targeting, that inspires innovation and may lead to improved vaccines,” said co-corresponding author Michael Zwick, associate professor of immunology and microbiology at the Scripps Research Institute.

HIV’s envelope presents a particularly difficult target for vaccine development, Zwick added, because the virus displays so few spikes and camouflages them with sugar molecules so as to evade our immune system.

“All these features increase the dynamic variability that the HIV spike protein presents to the immune system,” said Lee, who also directs a UW lab exploring virus structure and dynamics. “This is something that people in HIV vaccine development have grappled with from the very beginning — this virus mutates and changes itself astronomically and rapidly. Each time it infects an individual, you end up with literally thousands of different variants within that one individual, and if you look across populations, it’s multiplied even more.”

In fact, in February, an even more deadly strain of HIV was found to have been circulating in the Netherlands. Luckily, while the strain is a “highly virulent variant,” it still responds to treatment.

“This is just another reminder that these viruses are always changing, so we need scientists to continue studying them,” Zwick said.

Co-authors are Vidya Mangala Prasad, former acting instructor at UW School of Pharmacy, currently at the Indian Institute of Science; Daniel Leaman, Department of Immunology and Microbiology, The Scripps Research Institute; Klaus Lovendahl, Jacob Croft and Edgar Hodge, Department of Medicinal Chemistry, UW School of Pharmacy; and Mark Benhaim, who worked on the project as a graduate student at UW.

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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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