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Recalculating: when research starts one way and ends another

From medicine to geology to archaeology, sometimes science takes an unexpected turn into uncharted territory

We’re always told that the journey is just as important as the destination. This is true in many aspects of life, but perhaps nowhere as much as in scientific research. Flexibility, curiosity, and attention to detail can lead to a treasure you weren’t even expecting to find. TAU’s scientists talk about research that began one way and ended another, thanks to a few surprises along the way. A treasure in a pot A team of archeologists on an excavation mission found that sometimes, the appearance of a clay pot is no indication of its contents. “On one of the excavations in Megiddo, we removed the partitions separating the different sections of the dig and found a whole clay pot full of dirt,” says Naama Walzer, a doctoral student in the Department of Archeology and Early Eastern Cultures at Tel Aviv University. “We packed it up and planned to send it to a molecular residue lab to find out what used to be stored inside of this pot, which we dated to around 1100 BCE.” The pot was stored in an office, but after a while it became clear that preservation in that area of the excavation wasn’t up to standard, so the team decided to empty the pot, in a controlled way, and poured out its contents on the table. “We weren’t expecting to find what ended up being inside: a treasure trove of jewelry, considered one of the greatest troves found in Israel from the Biblical period!”   The pot discovered in Megiddo. (Photo courtesy of the Sonia and Marco Nadler Archeology Institute) Among other things, the trove contained nine large earrings and a seal ring, over a thousand small gold beads, and silver necklaces and jewelry. “This is how we found the big treasure of Area H, which is now part of the permanent exhibition at the Israel Museum in Jerusalem,” concludes Walzer.   Earrings, rings and gold beads. A huge treasure from the Biblical period. (Photo courtesy of the Sonia and Marco Nadler Archeology Institute) The longest record in the lowest place We’ve all heard that still water runs deep, but did you know it can run deep enough to be remembered hundreds of thousands of years later? “I was looking for places to sample a rock that sank, in a still setting, to the bottom of the Dead Sea,” recalls Prof. Shmulik Marco, head of the Porter School of the Environment and Earth Sciences. “The goal was to measure the magnetic properties of the rock in order to reconstruct the changes that have occurred in the Earth’s magnetic field. This information is essential to understanding one of the most important mysteries in geology. Scientists still have no satisfactory explanation for the mechanism that causes changes in the magnetic field, such as surprising reversals or constant changes in the position of the magnetic poles. While sampling the rocks, I found layers that looked “messy”. The study took an unexpected turn when I realized the “mess” was the result of earthquakes, and that became the main focus of the research.”   The lowest place: layers of rock at the Dead Sea Because modern seismographs have only existed for about a century, which is barely a moment in earthquake terms, it’s impossible to know how a specific area behaves over long periods of time. In Israel, for example, there’s documentation from the Biblical period (about 3,000 years ago), which is still considered very little. “But now we have a record of the earthquakes that happened around the Dead Sea in the last 220,000 years. That’s considered a unique, world record, because there’s no other documentation in the world that’s so long and continuous,” concludes Professor Marco.   Neat vs messy: A layer of rock in which the natural order was disturbed A miracle of light As she was nearing the end of her postdoctoral studies at Yale University, Dr. Ines Zucker of the Iby and Aladar Fleischmann Faculty of Engineering decided to advise an undergraduate student in a promising, short-term study. But as we all know, the only thing you can count on in life is that everything changes: “The purpose of the study was to show a difference in damage to liposomes (microscopic spheres filled by fluorescent fluid and surrounded by a membrane, used in medicine and in scientific studies of biological membranes) by a nanomatter called MnO2, produced in various structures,” explains Dr. Zucker. “In the past, we’ve shown a fluorescent fluid leak (i.e., liposome damage) was dependent on the surface of the nanomatter, and this time we wanted to show it also depended on its structure. But… research has its own rules – we couldn’t find the kind of damage we were looking for. Right as we were about to give up on the study, we took the system to a fluorescence microscope, where we saw that the liposomes and the nanomatter interact in a way we’ve never seen before in this context: the liposomes envelop the nanomatter, but remain whole, intact spheres without leakage! It was like a miracle of light.”   “Many times unexpected discoveries surprise us.” Dr. Zucker in the lab A star (re)born For Dr. Iair Arcavi, of the Department of Astrophysics at the Raymond and Beverly Sackler Faculty of Exact Sciences, a routine evening of surveying space through a robotic telescope led to discovering a brand new phenomenon: the resurrection of a star. “A few years ago, we came across a ‘star that didn’t want to die’ and kept exploding again and again,” Dr. Arcavi says. “Every night the telescope would find lots of new things, most of them uninteresting. Even with this supernova (which is a star that exploded), we initially thought it was uninteresting, because when the survey first caught it, it was in the dimming stage, and we thought we’d missed the interesting part. We noticed for weeks that the supernova was starting to get bright again, which is something that shouldn’t happen, so that piqued our interest and made us follow the supernova with additional telescopes.”   A supernova exploding far, far away “Usually, when a star explodes, the light intensity goes up and down and eventually disappears after a few months. In our case, the light intensity went up and down, then did it again and again, for a total of five times over two years. What surprised us even more was when we discovered that this star actually exploded in 1954, and after a star explodes, it’s not supposed to explode again, because the explosion destroys the star. To this day no one’s been able to explain it, and we haven’t seen a similar event since.”   The sky is full of surprises: Dr. Arcavi and the Hawaii observatory Two for the price of one Have you ever looked for a solution to a problem, only to solve an entirely different problem along the way? That’s exactly what happened to Prof. Noam Shomron of the Sackler School of Medicine. “We wanted to develop a way to identify a specific disease, but along the way we discovered more options, so we made those additional targets of the research,” he says. “We tracked thousands of pregnant women, to characterize blood molecules that can be early markers of preeclampsia, a condition that can only occur after the 20th week of pregnancy. Not only did we find those molecules, we also managed to characterize other molecules, that could be an indicator of gestational diabetes.” (There’s no connection between the two conditions, except that they both occur during pregnancy.) “What’s exciting about this story is that there’s still no way of identifying, in the first trimester, using a simple blood test, problems that can occur in the second or third trimester. But our discovery will allow simple blood tests to be developed to identify both conditions, which will then lead to preventative measures at an early stage, and ensure the wellbeing of both mother and baby.”   Professor Shomron talking about his accidental discovery at an “Atnahta” event at TAU

Human body parts ‘on-a-chip’ could revolutionize drug testing

A new system will drastically shorten the time it takes to develop safe and effective medication

The U.S. Food and Drug Administration (FDA) approves only 13.8% of all tested drugs, and these numbers are even lower in “orphan” diseases that affect relatively few people. Part of the problem lies in the imperfect nature of preclinical drug testing that aims to exclude toxic effects and predetermine concentrations and administration routes before drug candidates can be tested on people. How new drugs move within the human body and are affected by it, and how drugs affect the body itself, cannot be predicted accurately enough in animal and standard in vitro studies. “To solve this massive preclinical bottleneck problem, we need to become much more effective at setting the stage for drugs that are truly promising and rule out others that for various reasons are likely to fail in people,” explains Prof. Donald Ingber, M.D., Ph.D., founding director of Harvard University’s Wyss Institute for Biologically Inspired Engineering, co-author of two new studies on the subject published in Nature Biomedical Engineering. Co-led by Dr. Ben Maoz of Tel Aviv University’s Department of Biomedical Engineering and Sagol School of Neuroscience and over 50 colleagues, a team of scientists at TAU and Harvard have now devised a functioning comprehensive multi-Organ-on-a-Chip (Organ Chip) platform that enables effective in-vitro-to-in-vivo translation (IVIVT) of human drug pharmacology.

Testing on humans, without humans

“We hope that this platform will enable us to bridge the gap on current limitations in drug development by providing a practical, reliable, relevant system for testing drugs for human use,” says Dr. Maoz, co-first author of both studies and former Technology Development Fellow at the Wyss Institute on the teams of Prof. Ingber and Prof. Kevin Kit Parker, Ph.D., the latter of whom is also a leading author of both studies. In the first of two studies, the scientists developed the “Interrogator,” a robotic liquid transfer device to link individual “Organ Chips” in a way that mimics the flow of blood between organs in the human body. Organ Chips are microfluidic devices composed of a clear flexible polymer the size of a computer memory stick that contains two parallel running hollow channels separated by a porous membrane and independently perfused with cell type-specific media. While one of the channels, the parenchymal channel, is lined with cells from a specific human organ or functional organ structure, the other one is lined with vascular endothelial cells presenting a blood vessel. The membrane allows the two compartments to communicate with each other and to exchange molecules like cytokines and growth factors, as well as drugs and drug products generated by organ-specific metabolic activities. The team then applied their Interrogator automated linking platform and a new computational model they developed to three linked organs to test two drugs: nicotine and cisplatin.

Liver on a chip

“The modularity of our approach and availability of multiple validated Organ Chips for a variety of tissues for other human Body-on-Chip approaches now allows us to develop strategies to make realistic predictions about the pharmacology of drugs much more broadly,” says Prof. Ingber. “Its future use could greatly increase the success rates of Phase I clinical trials.” The researchers accurately modeled the oral uptake of nicotine and intravenous uptake of cisplatin, a common chemotherapy medication, and their first passage through relevant organs with highly quantitative predictions of human pharmacokinetic and pharmacodynamic parameters. “The resulting calculated maximum nicotine concentrations, the time needed for nicotine to reach the different tissue compartments, and the clearance rates in the Liver Chips in our in vitro-based in silico model mirrored closely what had been measured in patients,” concludes Dr. Maoz. The multidisciplinary research project is the culmination of a Defense Advanced Research Projects Agency (DARPA) project at the Wyss Institute. Several authors on both studies, including Prof. Ingber, are employees and hold equity in Emulate, Inc., a company that was spun out of the Wyss Institute to commercially develop Organ Chip technology.

New study reveals palace bureaucracy in ancient Samaria

Researchers find different inscriptions were penned by the same author, bringing together math, physics and archaeology

The ancient Samaria ostraca — eighth-century BCE ink-on-clay inscriptions unearthed at the beginning of the 20th century in Samaria, the capital of the biblical kingdom of Israel — are among the earliest collections of ancient Hebrew writings ever discovered. But despite a century of research, major aspects of the ostraca remain in dispute, including their precise geographical origins — either Samaria or its outlying villages — and the number of scribes involved in their composition. A new Tel Aviv University study found that just two writers were involved in composing 31 of the more than 100 inscriptions and that the writers were contemporaneous, indicating that the inscriptions were written in the city of Samaria itself. Research for the study was conducted by Ph.D. candidate Shira Faigenbaum-Golovin, Dr. Arie Shaus, Dr. Barak Sober and Prof. Eli Turkel, all of TAU’s School of Mathematical Sciences; Prof. Eli Piasetzky of TAU’s School of Physics; and Prof. Israel Finkelstein, Jacob M. Alkow Professor of the Archaeology of Israel in the Bronze and Iron Ages, of TAU’s Sonia and Marco Nadler Institute of Archaeology.

A palace bureaucracy

The inscriptions list repetitive shipment details of wine and oil supplies to Samaria and span a minimal period of seven years. For archaeologists, they also provide critical insights into the logistical infrastructure of the kingdom of Israel. The inscriptions feature the date of composition (year of a given monarch), commodity type (oil, wine), name of a person, name of a clan and name of a village near the capital. Based on letter-shape considerations, the ostraca have been dated to the first half of the eighth century BCE, possibly during the reign of King Jeroboam II of Israel. “If only two scribes wrote the examined Samaria texts contemporaneously and both were located in Samaria rather than in the countryside, this would indicate a palace bureaucracy at the peak of the kingdom of Israel’s prosperity,” Prof. Finkelstein explains. “Our results, accompanied by other pieces of evidence, seem also to indicate a limited dispersion of literacy in Israel in the early eighth century BCE,” Prof. Piasetzky says.

When math solves history

“Our interdisciplinary team harnessed a novel algorithm, consisting of image processing and newly developed machine learning techniques, to conclude that two writers wrote the 31 examined texts, with a confidence interval of 95%,” said Dr. Sober, now a member of Duke University’s mathematics department. Prof. Israel Finkelstein at a TAU dig in Megido “The innovative technique can be used in other cases, both in the Land of Israel and beyond. Our innovative tool enables handwriting comparison and can establish the number of authors in a given corpus,” adds Faigenbaum-Golovin. The new research follows up from the findings of the group’s 2016 study, which indicated widespread literacy in the kingdom of Judah a century and a half to two centuries later, circa 600 BCE. For that study, the group developed a novel algorithm with which they estimated the minimal number of writers involved in composing ostraca unearthed at the desert fortress of Arad. That investigation concluded that at least six writers composed the 18 inscriptions that were examined. “It seems that during these two centuries that passed between the composition of the Samaria and the Arad corpora, there was an increase in literacy rates within the population of the Hebrew kingdoms,” Dr. Shaus says. “Our previous research paved the way for the current study. We enhanced our previously developed methodology, which sought the minimum number of writers, and introduced new statistical tools to establish a maximum likelihood estimate for the number of hands in a corpus.”

Featured Image: Inscriptions on pottery fragments from Samaria, the capital of Israel, with added color. The inscriptions date to the first half of the 8th century BCE. (photo: Harvard Semitic Museum)

TAU’s new center will combine medicine and food security

A new center for plant sciences, in partnership with Adama, will train the next generation of experts in delivery and formulation, key aspects of modern agriculture

Tel Aviv University and Adama, one of the leading companies in plant protection, have launched a unique research and teaching program in the field of delivery (the stage of transporting and linking the active substance to its target site in weeds or agents harmful to plants) and formulation, which is a growth and innovation engine in the field of food, agriculture and plant protection. The innovative curriculum will be taught at the “Adama Center for Advanced Transportation Systems for Plant Protection Materials”, at the School of Chemistry, in collaboration with the School of Plant Sciences and Food Security and the Sackler Faculty of Medicine at Tel Aviv University. As part of the program, researchers and students will be acquiring advanced degrees in Israel and abroad.

Adama offers farmers effective solutions and services for dealing with weeds, pests and lesions and improving their crops. About a year ago, the company inaugurated an innovative research and development center in Neot Hovav, which houses more than 100 researchers. Dozens of collaborations are being conducted at the center with researchers and academics specializing in chemistry, agronomy, agriculture and other fields. Dr. Elad Shabtai, VP of Innovation, Research, Development and Licensing at Adama, explains that until now, delivery and formulation expertise was usually acquired only through working in the industry, and one couldn’t study the field or gain experience through any academic setting in the world. This has created a growing shortage of experts in the field.

The unique curriculum developed by Tel Aviv University and the Adama research and development team will integrate the world of industry and academia, expose students to the field of delivery and formulation, and train the next generation of experts. In addition, Adama will invest in a world-class research lab, set up at the School of Chemistry, where studies and experiments will be conducted. Adama will provide scholarships to approximately 25 students from a variety of fields such as chemistry, materials engineering, plant sciences and more. Students will gain access to advanced soil labs to conduct experiments and undergo practical training by researchers from the company.

Significant connection between academia and industry

At the signing ceremony, held at the company’s research and development center in Neot Hovav, Dr. Chen Lichtenstein, president and CEO of Adama said: “Adama understands that its success in the global, competitive market rests on research and development capabilities as a vehicle for strategic growth. The international center for delivery and formulation that we’re launching at Tel Aviv University will enable us to train the best researchers in the field, and prepare them for entry into the agrochemical industry, so they can develop products that meet the world’s agricultural challenges. “

Prof. Ariel Porat, President of Tel Aviv University, said at the ceremony: “Tel Aviv University attaches great importance to the development of applied research, along with baseline research. To this end, it collaborates with various industries, in various fields. The cooperation with Adama, which we are very pleased about, will contribute much to the advancement of research and teaching in the fields of chemistry, food, agriculture and plant protection, and will benefit the State of Israel.”

Dr. Elad Shabtai, VP of Innovation, Research, Development and Licensing, emphasized: “The connection and ties between academia and industry are significant and central in the context of research and development. We must work to train and strengthen researchers and scientists in the field, starting with the academic stage, to provide a basis for inventions and development.”

Prof. Roey Amir, from the School of Chemistry and head of the Adama Center for Advanced Delivery Systems for Plant Protection Materials at Tel Aviv University, said: “In recent years there has been a demand for smart agriculture development, which will minimize the amount of plant protection materials while improving their operation through advanced delivery systems, similarly to what’s happening in biomedical research. Opening the center will allow us to work together with Adama to train the future generation of scientists who will lead the field in Israel and around the world.”

Siblings of children with intellectual disabilities better at empathy, teaching

TAU research suggests positive impact of relationships between children and their siblings with intellectual disabilities

The sibling relationship is the longest most people will enjoy in their lifetimes and is central to the everyday lives of children. A new Tel Aviv University and University of Haifa study finds that relationships between children and their siblings with intellectual disabilities are more positive than those between typically developing siblings. The research examines the relationships of typically developing children with siblings with and without intellectual disabilities through artwork and questionnaires. It was conducted by Prof. Anat Zaidman-Zait of the Department of School Counseling and Special Education at TAU’s Constantiner School of Education and Dr. Dafna Regev and Miri Yechezkiely of the University of Haifa’s Graduate School of Creative Art Therapies. The study was recently published in Research in Developmental Disabilities. “Having a child with a disability in a family places unique demands on all family members, including typically developing siblings,” Prof. Zaidman-Zait explains. “Although challenges exist, they are often accompanied by both short- and long-term positive contributions.

More empathy, less fighting

“Through our research, we found that relationships among children with siblings with intellectual disabilities were even more supportive than those among typically developed siblings. Specifically, we found that children with siblings with intellectual disabilities scored higher on empathy, teaching and closeness and scored lower on conflict and rivalry than those with typically developing siblings.” Until now, research on how having a sibling with a developmental disability affects children’s social-emotional and behavioral outcomes generated mixed findings. At times, the findings suggested that having a sibling with developmental disabilities led to greater variability in typically developing children’s behavior and adjustment. “But these studies did little to tap into the inner worlds of children, which really can only be accessed through self-expression in the form of art or self-reporting, independent of parental intervention, which is the route we took in our study,” Prof. Zaidman-Zait says.

Measuring relationships through art

The scientists assessed some 60 children aged 8-11, half with typically developing siblings, half with intellectually disabled siblings, through drawings and a questionnaire about their relationships with their siblings. Mothers of both sets of siblings were also asked to answer a questionnaire about their children’s sibling relationship quality. “We drew on the basic assumption that artistic creation allows internal content to be expressed visually and that children’s self-reports have special added value in studies measuring sibling relationship qualities, especially in areas where parents might have less insight,” Prof. Zaidman-Zait says. Both sets of typically developing children, with and without siblings with intellectual disabilities, were asked to draw themselves and their siblings. Licensed art therapists then used several set criteria to “score” the illustrations: the physical distance between the figures; the presence or absence of a parent in the illustration; the amount of detail invested in either the self-portrait or the sibling representation; and the amount of support given to a sibling in the picture. The children were then asked to complete the Sibling Relationship Questionnaire, which assessed the feelings of closeness, dominance, conflict and rivalry they felt for their siblings. Reviewing the children’s illustrations and questionnaires, as well as the questionnaires completed by the children’s mothers, the researchers found that the children with siblings with intellectual disabilities scored significantly higher on empathy, teaching and closeness in their sibling relationship and scored lower on conflict and rivalry in the relationships than those with typically developing siblings. “Our study makes a valuable contribution to the literature by using an art-based data gathering task to shed new light on the unique aspects of the relationships of children with siblings with intellectual disabilities that are not revealed in verbal reports,” Prof. Zaidman-Zait concludes. “We can argue that having a family member with a disability makes the rest of the family, including typically developing children, more attentive to the needs of others.” The researchers hope their study, supported by The Shalem Foundation in Israel, will serve as a basis for further research into art-based tools that elicit and document the subjective experience of children.

TAU study among top 12 most important in the world

Prof. Yoel Rak’s anthropology study was selected by Science Magazine as one of the scientific breakthroughs of the 2019

Each year, Science Magazine, arguably the world’s most prestigious scientific publication, selects 12 groundbreaking studies from around the world, inviting the public to vote for whichever study they consider the most important. This year, the list includes an Israeli study, done in collaboration with Prof. Yoel Rak, a physical anthropologist from the Sackler Faculty of Medicine, led by researchers from the Hebrew University of Jerusalem, in which scientists were able to reconstruct a human profile of a mysterious group known as the Danisovans, using DNA remnants only.

Who are the Denisovans?

The Denisovans are a group of humans who lived in the east and northeast of Asia until a few tens of thousands of year ago, and differed in their characteristics from the Homo sapiens and Neanderthals who were alive at the time. While the Homo sapiens lived mainly in Africa at that time, the Neanderthals settled in Europe and North Asia, where they met with the Danisovans and mixed with them. Until recently, all of our knowledge about this group was based on a few small pieces of bone, and it is believed that the group’s existence would not have been uncovered except for the development of new methods for the extraction, sequencing and analysis of ancient DNA.

The study by Prof. Rak and his colleagues presented an exciting breakthrough: the restoration of a Denisovan’s face using an epigenetic reconstruction method of ancient DNA, taken from the tip of a young woman’s finger, which was found in Siberia in 2008. This is a study of genetic changes that do not occur in the sequence of DNA letters itself, but affect how genes are expressed in each and every cell.

The study will make it possible to understand the various adaptations made by the Danisovans group to its surroundings, and shed light on features that distinguish us, modern humans, from the other human groups that did not survive to modern times.

Alongside Prof. Rak’s study, the competition at Science also included the first photograph of a black hole, a photo of the space rock Ultima Thula, the skeleton of “Lucy’s” ancestor from 3.8 million years ago, long-term treatment for the HIV virus and other studies from the world of medicine.

Making the future accessible

For International Braille Day we talked to the head of TAU’s Sourasky Central Library about the future of accessibility

For many years, if you were vision impaired and wanted to read, you had to know Braille. Invented by Louis Braille, this unique form of tactile writing was introduced to the world in the 1830s and revolutionized access to information for people with visual disabilities. It allowed people the freedom to study, work, earn wages, and live independently, where before these options were extremely limited. By 1960, it was estimated that about 50% of children who were legally blind could read braille in the United States.

But in today’s digital age, new forms of accessibility have become more widespread. We wanted to find out – is Braille still relevant or on its way to becoming extinct?

From text to voice When we asked the staff at TAU’s Sourasky Central Library about books in Braille, we realized we were asking the wrong questions. The library doesn’t have any Braille books, investing instead of more modern forms of accessibility.

 “We see accessibility as a very important issue,” says Naama Scheftlowitz, director of the Sourasky Central Library. “But Braille isn’t the most efficient solution these days. We offer students with disabilities more advanced forms consuming text, such as text-to-voice programs and audiobooks. Another benefit is that these forms of accessibility help not just vision-impaired people, but a wide range of students and library patrons. For example, students who don’t speak Hebrew and have difficulty reading, but listening makes it easier for them to study.”

Audio is the future

Every computer at the library comes equipped with “Kolfix”, a text-to-voice program that can read any text on the screen out loud for the user. The library also offers students a subscription to iCast, an Israeli company that provides audiobooks, including translations of foreign books into Hebrew. The library’s search engine, DATA, also has a brand new feature that allows users to “voice search”, meaning to say the search term into a microphone instead of having to type it out.

Putting accessibility in the center

In the lobby of the library lives the Mia and Mila Pinkas Accessibility and Learning Assistance Center, maintained by the Dean of Students. Being placed in the lobby of the building means it’s centrally located on campus, and the library is right there for any assistance. It’s a spacious area containing work stations with advanced technological equipment, including magnification and reading software, and ergonomic equipment, aimed at making studying as accessible as possible for students with disabilities.

Some of the work stations at the Mia and Mila Pinkas Accessibility and Learning Assistance Center

“The very fact that the Accessibility Center is located within the library,” Naama says, “raises awareness of the issue, and we keep up to date with new technologies and adopt them. We even serve as an address for various inquiries to assist with complex student needs.”

TAU study finds widespread misinterpretation of gene expression data

Bias can be now be removed from data to filter out false results, researchers say

Reproducibility of research data is a major challenge in experimental biology. As data generated by genomic-scale techniques increases in complexity, this concern is becoming more and more worrisome. RNA-seq, one of the most widely used methods in modern molecular biology, allows in a single test the simultaneous measurement of the expression level of all genes in a given sample. New research by a Tel Aviv University group identifies a frequent technical bias in data generated by RNA-seq technology, which often leads to false results. The study was conducted by Dr. Shir Mandelbaum, Dr. Zohar Manber, Dr. Orna Elroy-Stein and Dr. Ran Elkon at TAU’s Sackler Faculty of Medicine and George S. Wise Faculty of Life Sciences and was published on November 12 in PLOS Biology. “Recent years have witnessed a growing alarm about false results in biological research, sometimes referred to as the reproducibility crisis,” Dr. Elkon, lead author of the study, says. “This study emphasizes the importance of proper statistical handling of data to lessen the number of misleading findings.”

Removing bias from science

A main goal of RNA-seq experiments is to characterize biological processes that are activated or repressed in response to different conditions. The researchers analyzed dozens of publicly available RNA-seq datasets to profile the cellular responses to numerous stresses. During the research, the scientists noticed that sets of particularly short or long genes repeatedly showed changes in the expression level measured by the apparent number of RNA transcripts from a given gene. Puzzled by this recurring pattern, the team wondered whether it reflected some universal biological response common to different triggers or whether it stemmed from some experimental condition. To tackle this question, they compared replicated samples from the same biological condition. Differences in gene expression between replicates can reflect technical effects that are not related to the experiment’s biological factor of interest. Unexpectedly, the same pattern of particularly short or long genes showing changes in expression level was observed in these comparisons between replicates. This pattern is the result of a technical bias that seemed to be coupled with gene length, the researchers say. Importantly, the TAU researchers were able to show how the length bias they detected in many RNA-seq datasets led to the false identification of specific biological functions as cellular responses to the conditions tested. “Such misinterpretation of the data could lead to completely misleading conclusions,” Dr. Elkon concludes. “In practical terms, the study also shows how this bias can be removed from the data, thus filtering out false results while preserving the biologically relevant ones.”

Fibroblasts involved in healing spur tumor growth in cancer

Vital to healing wounds, fibroblasts have a “misguided” response to cancer cells, according to TAU researchers

The connective tissue cells known as fibroblasts are vitally important for our recovery from injury. Sensing tissue damage, they gravitate to the site of a wound, instigating an inflammatory response that mends damaged tissue. A new Tel Aviv University study published in Nature Communications finds that fibroblasts also play a devastating role in the development of breast cancer. In cancer tumors, fibroblasts are triggered to respond to tissue damaged by tumors and create inflammation. This inflammation facilitates tumor growth as well as metastases in the lungs. “We have shown, for the first time, that in breast cancer these fibroblasts activate a ‘misguided’ wound healing response, responding to the tissue damage caused by the cancerous growth,” explains Prof. Neta Erez of TAU’s Sackler Faculty of Medicine, who led the research for the study. “Inhibiting these inflammatory signaling pathways may be beneficial in preventing metastatic relapse of breast cancer.” The study was conducted by former TAU student Yoray Sharon and TAU MD-PhD student Nour Ershaid in Prof. Erez’s lab at TAU’s Department of Pathology.

When tumors “hijack” repair functions

According to the study, the inflammatory response of fibroblasts not only supports local tumor growth in the breast, but it also creates a hospitable niche for metastatic growth in the lungs. “The fibroblasts are ‘activated’ and, because of this activation, they recruit immune cells and affect blood vessels,” adds Prof. Erez. “In other words, breast tumors ‘hijack’ the physiologic response to tissue damage to facilitate their growth, and create a niche in a distant organ, the lungs, by ‘remote control.'” Research for the study was performed using transgenic and transplantable mouse models of breast cancer, and validated in human samples of breast cancer and in human expression data. The researchers isolated fibroblasts in transgenic mice from different stages of breast carcinogenesis and profiled the expression of all their genes. They were then able to identify that the inflammation pathway is unregulated in cancer-associated fibroblasts, as compared with fibroblasts isolated from normal mammary glands. Finally, they performed functional experiments to understand the role of this pathway in breast cancer. “Our findings encourage the design of preclinical and clinical studies to examine the benefits of targeting the inflammation pathway in breast cancer, which may be effective in blocking metastatic relapse,” concludes Prof. Erez. “We are now studying the microenvironment of metastasis in an effort to identify targets for preventive intervention that may inhibit metastatic relapse.”

Bringing water to Tanzania

Tel Aviv University’s future engineers flew to Africa to connect a school with 1,000 students to clean water

The children living in the villages of Babati district, Tanzania will now have drinkable water during the dry season, thanks to the student delegation from the Iby and Aladar Fleischman Faculty of Engineering. Unfortunately, there are still many places in the world where fresh, clean water, which many in developed countries take for granted, is a rare commodity. This is a common problem in many African countries. Each year, a delegation of engineers from the University of Tanzania sets out to build and improve water and electricity infrastructure. They do so within the framework of the “Engineers Without Borders” association, which works to promote and improve the quality of life of the Israeli population and developing populations worldwide. This year, as in previous years, students responded to the organization’s call, and a delegation of six students flew out during the Sukkot holiday break to contribute their time and knowledge, gained during their studies, and install systems at the regional school that would store 40,000 liters of water.

Months without water

“In Babati district, children sometimes have to walk 10 kilometers to reach clean water reservoirs, or settle for stagnant, contaminated water containing high levels of fluoride, which is detrimental to their health,” says Natalie Lubelchick, a University delegation graduate who is currently completing her master’s degree in Astrophysics. In Tanzania, during the dry season, the local rural population has to cope with three long, hot and dry months. In the absence of a solid infrastructure, the search for drinkable water sources is particularly difficult. If that’s not enough, the same water is also sought by wild animals, who often damage the few existing artificial water reservoirs. The mission of the Israeli delegation, which has sent volunteers for the fifth time, was to build a 40,000-liter water collection system from the rooftops of the Babati district school, where approximately a 1,000 students study, maintain existing systems installed by previous delegations, and also establish a new library, together with the local community. The project is overseen by Prof. Dror Avisar, head of the Water Research Center.   Working together: members of the delegation with locals from the school in Babati district Working together: members of the delegation with locals from the school in Babati district

A glass of water a day for 1,000 children

After a 12-hour flight and before they embarked on two weeks of challenging physical labor, the delegation acquired all the necessary equipment they didn’t bring with them from Israel in Arusha, the city where they landed: dozens of huge 2000-liter containers, each to be installed in a school, as well as pipes and work tools. The main difficulty of this delegation and its predecessors is in being funded. “The ideal situation is that we would have a regular annual budget and know that our operations are guaranteed,” explains Natalie. Sometimes it’s unclear until the day of departure how much money will be at their disposal. On the eve of leaving the city for the village, the delegation members met the Tanzanian community representative, Julius, a school teacher who accompanies the project, and met his family. “He is the delegation’s angel and takes care of all of us,” says Natalie.   Smiles all around: Julius and his family with members of the delegation Smiles all around: Julius and his family with members of the delegation At the biggest, most central school in Babati district, where the largest system was about to be installed, the delegation was greeted with an enthusiastic welcome. Knowing that soon every student would be able to enjoy clean water was exciting for the children.   Hope and excitement: the delegation is recieved by the young students Hope and excitement: the delegation is recieved by the young students   At the principal's office​ At the principal’s office The first order of business for the delegation was teaching a group of boys and girls from local Scouts how to help with the construction and then later on how to maintain the systems. “The idea is not just to build a system, but to work collaboratively with the community, which includes education and instruction, which will lead to long-term results,” Natalie explains. Left: local Scouts learning the new system. Left: children from the school using it to get clean water. Left: local Scouts learning the new system. Right: children from the school using it to get clean water.   The construction process included installing gutters, cleaning the water tanks and preparing the infrastructure. In one of the schools, where systems had already been installed in the past, the delegation had to replace containers, destroyed by elephants that came in search of water, and build anti-elephant concrete walls around them.   While the systems were being installed, the delegation members taught the students about proper use of the system and “water discipline”, and in return the students taught them local songs and dances. Singing while you work: two members of the delgation with young students Singing while you work: two members of the delgation with young students When it was clear that the work was progressing quickly and efficiently, the delegation decided to visit local families and get to know the community. “We started asking them questions about their daily lives and their needs,” Natalie says. “We realized that in addition to building the systems in schools, we also want to think of a home solution. Most people here live in extended families, sometimes numbering up to 50 people. So, a solution for one family can spare them a walk to the nearest water source, which can take hours, and also give them clean water, as opposed to reservoirs that are very polluted. Our challenge was to think of a simple, creative and inexpensive solution, using local materials, so we could easily distribute and duplicate it, and they could easily maintain the systems.”     Sometimes the villagers are forced to drink polluted water Sometimes the villagers are forced to drink polluted water

As the largest system was assembled at the Minjingu Elementary School, the principal, together with the teachers, some of the parents and a thousand students, conducted a moving farewell ceremony. “They thanked us with a song, and promised to maintain the system, and we, for our part, got to see and understand how important the system is to them,” Natalie concludes.

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