Lactic acid is produced when the body breaks down carbohydrates in low oxygen levels to generate energy. It is mainly found in muscle cells and red blood cells. An example of lactic production is when we perform intense exercise.
Glucose, glutamine, fatty acids, and amino acids are well-known energy sources for cell growth and division. In the past, lactic acid has been known as a by-product of glycolysis, a process in which glucose is broken down through several enzyme reactions without the involvement of oxygen. However, recent studies showed that lactic acid is a key player in cancer cells to regulate tumor cell growth and division, blood vessel formation, and invasion. The tumor cells prefer to use glycolysis to produce energy and lactic acid despite the abundance of oxygen levels. Lactic acid is an alternative fuel source for glucose-deprived tumors to avoid cell death.
Lactic acid is transported through the membrane via the monocarboxylate transporter 1 (MCT1). A research group at Columbia University led by Dr. Markus Siegelin in the department of Pathology and Cell Biology showed a substantial presence of lactic acid in the citric acid cycle (TCA cycle), a series of chemical reactions to generate energy, in the glioblastoma cells cultured in the nutrient deprivation condition (low glucose and glutamine concentration). When the glucose and/or glutamine concentrations increased, less lactic acid was involved in the TCA-cycle metabolites. The uptaken lactic acid in the TCA-cycle was traced by using a method called C13 carbon tracing and was analyzed by liquid chromatography-mass spectrometry to identify the structure of different molecules. The researchers concluded that lactic acid is used as a fuel source to generate the energy in the brain tumor cells. Furthermore, lactic acid is converted to Actetyl-CoA and contributed to the gene modification in glioblastoma cells (Figure 1). These novel findings were published in a prestigious journal, Molecular Cell.
Figure 1: Role of lactic acid in the epigenetic modification of glioblastoma cells. Lactic acid is transported to the membrane via the monocarboxylate transporter 1 (MCT1) and contributed to the TCA cycle as a fuel source to generate the energy. Lactic acid is converted to Actetyl-CoA and contributed to the gene modification in glioblastoma cells. Suppressing the TCA cycle by using the targeted drug, namely CPI-613 (devimistat) leads to the abrogation of lactic acid in the energy production. The figure was generated by Biorender.
From these findings, the authors proposed to use CPI-613 (devimistat) drug, which targets TCA-cycle metabolites (Figure 1), to treat glioblastoma cells. Indeed, CPI-613 showed a suppression of cellular viability in vitro of glioblastoma cells and an extension of the animal survival curve in the mouse model. The authors suggested that the combination of CPI-613 with other standard care treatment in glioblastoma such as temozolomide and radiation could be a potential clinical therapy for patients with glioblastoma.
It is well-established that children growing up in economically disadvantaged circumstances can experience a wide variety of challenges to their development. For example, in the domain of language, psychological research shows that even before children reach the age of 3, those from lower socioeconomic (SES) backgrounds hear fewer and less complex words from caregivers compared to their more advantaged peers. This phenomenon places these children at risk of later language learning difficulties. Research groups and other stakeholders around the globe are working tirelessly to craft intervention programs, in a variety of contexts, to target the optimal development of children from under-resourced environments. To target language outcomes, for instance, an initiative called Talk With Me Baby aims to help parents learn about and engage in crucial linguistic interactions with their children from their earliest days.
One prominent intervention in this field is taking a different approach. The Baby’s First Years (BFY) project, directed by a team of leaders in the realms of neuroscience, psychology, and economics, provides families living in poverty with cash and is studying how this money might impact developmental outcomes. These scientists recruited 1,000 mothers from around the US just hours after their babies were born. Half of the mothers are assigned to a high-cash gift group ($333 per month) and the other half are assigned to a low-cash gift group ($20 per month). These payments come in the form of a debit card and the moms are allowed to spend these funds however they’d like.
The “4 My Baby” card, the debit card that BFY mothers receive. Courtesy of Baby’s First Years.
After one year of these payments, the researchers went into the homes of the families and measured a variety of both maternal and child outcomes. One of these measures was EEG, or electroencephalography, to capture the brain activity of the infants. EEG measures the electrical activity occurring between cells in the brain. The findings, published in a recent paper in PNAS by lead author and Columbia postdoc Dr. Sonya Troller-Renfree, captured global attention. She and her team found that infants whose mothers were assigned to the high-cash gift group displayed more high-frequency brain activity compared to children in the low-cash group. Importantly, previous research links this high-frequency activity to the development of thinking and learning. Although the evidence is not air tight, Dr. Troller-Renfree and her team are the first to show there may be a causal link between poverty reduction and changes in brain activity.
There are many pathways through which the gifted money might be impacting children’s brains, which is currently under investigation. It is important to understand that this study is still ongoing and the children in the sample are all currently around 3-years-old. The research team plans to assess the mothers and preschoolers at age 4 on a variety of outcomes. This finding on the potential link between poverty reduction and the brain, along with other work demonstrating that economic support for parents could greatly benefit children’s outcomes, has important implications for public policies that support families and children. While the US has a long way to go in supporting its youth, growing evidence indeed supports the idea that relatively minor investments in children can positively impact their trajectory.
Dr. Sonya V. Troller-Renfree is a Goldberg Postdoctoral Fellow in the Neurocognition, Early Experience and Development Lab at Teachers College, Columbia University. Her research focuses on the effects of early adversity and poverty on cognitive and neural development. She intends to continue examining these questions as part of her new, federally-funded Pathway to Independence Award (K99/00). You can stay up-to-date on her research findings on Twitter at @STRscience or on her website: www.sonyatrollerrenfree.com.
Over the last two years, the SARS-CoV-2 (Covid-19) pandemic has been at the forefront of media coverage. Hospitals have been overwhelmed, full cities locked down, travel banned, and we are all desperately waiting for a return to the normalcy that immunity promises. However, the development and retention of immunity can be dependent on the individual, and Covid-19 has been particularly daunting to individuals with weakened immune systems (people who are immunocompromised). These individuals are at an increased risk of succumbing to Covid-19. Overall, it has been easy to identify the individuals that fall into this risk category. However, there has been limited research on the immunity of individuals that have undergone organ transplants. In a new article by Dr. Mithil Soni, researchers have identified the effects of a solid organ transplant (SOT) on the development and retention of immunity to a plethora of viruses including SARS-CoV-2. SOTs are transplants that include the kidney, liver, heart, lungs, intestines, and pancreas .
Dr. Soni and colleagues also focus on the immunity generated by T cells, or cells beyond antibodies that play a role in killing viruses that enter the body. In this study, they focused on the immune response of one patient, a 33-year old male suffering from erythropoietic protoporphyria, a genetic metabolic disorder that results in excessive liver damage. This subject underwent a SOT and received a liver. When undergoing a SOT, individuals are usually put through a stringent course of immunosuppressants to prevent organ rejection, which places them in the category of immunocompromised. To their surprise, during a check-up this patient was found to have antibodies for SARS-CoV-2, indicating a previous Covid-19 infection without any serious symptoms. The ability to overcome Covid-19 with minimal symptoms while being classified as immunocompromised intrigued Dr. Soni and colleagues, and the patient agreed to provide his blood for further testing.
The team went on to test the patient’s immune response to many infections that usually impact immunocompromised individuals. They tested the blood’s immune response to cytomegalovirus and BK virus, two viral infections that immunocompromised and SOT patients are prone to. They also tested the response to Epstein-Barr virus, which can cause Mononucleosis. From the blood, Dr. Soni and colleagues were able to collect and grow the T cells in their lab, exposed them to viruses, and measured their release of cytokines, proteins that are important for a strong immune response. They found a very strong T cell immune response against both cytomegalovirus and BK virus. They also tested the immune response to SARS CoV-2 and other coronaviruses and found a similar level T cell immune response as seen with cytomegalovirus and BK virus.
These findings overall indicated that the SOT patient continued to have a robust immune response to multiple viruses despite the immunocompromised status. This study shows that it is possible to have robust immune responses to viruses including SARS CoV-2 in an immunocompromised state such as seen after a SOT. However, this research is based on a single case study. To truly understand T-cell memory and activity in immunocompromised individuals much more research has to be done. This means Dr. Soni and colleagues still have their work cut out for them and are actively expanding the research done here. Their next immediate steps are to repeat this study with blood from a larger group of healthy and immunocompromised individuals in the hopes that they will eventually be able to answer the question of SOT and immunity.
Figure: Depiction of increased immunity after SOT. Top: Liver transplant. Bottom: Expected T cell activity in response to virus vs actual T cell activity in response to virus.
Dr. Mithil Soni, is a previous Postdoctoral Research Fellow and current Associate Research Scientist at Columbia University.
When it comes to cancer, one molecule stands out as being among the most extensively studied: the p53 tumor suppressor protein. p53 can exist in cells in several different forms. When p53 is in its so-called wild-type form, it is capable of activating various responses that contribute to tumor suppression. In their recent review, Columbia postdoc Rafaela Muniz de Quieroz and colleagues summarize the vast scientific literature on two key regulators of p53: MDM2 and MDMX. Both MDM2 and MDMX are known to interact with p53 and disrupt its function. Their absence has been linked not only to increased cancer development, but also to a number of dysfunctions, including embryonic lethality in mice. MDM2 has been shown to negatively regulate p53 by diverse mechanisms spanning from expression of the p53 gene to degradation of the p53 protein or its expulsion from the cellular nucleus, where the protein accomplishes its function. Although very similar to MDM2, MDMX is less well studied. We do know, however, that MDMX is a protein that can work together with the MDM2 in p53 degradation.
While many reviews and studies have pointed to the roles of MDM2, and to a lesser extent of MDMX, in p53 regulation, the current review by Quieroz and her colleagues puts a larger focus on the myriad of p53-independent activities of MDM2 and MDMX. The authors provide important details about the p53-independent functions of both MDMX alone and as part of a MDM2–MDMX complex. The review discusses some key features in the structure and function of the proteins, including key parts that are relevant for their function, for some associated abnormalities, or for the formation of MDM2 and MDMX complexes.
MDM2 and MDMX are regulated on multiple levels within cells. These include regulation on the DNA level, including usage of several alternative promoters (DNA sequences needed to turn a gene on or off). One of the promoters of MDM2 and MDMX is regulated by their target p53, but there are also p53-independent promoters capable of switching on the genes of MDM2 and MDMS regardless of p53. In addition, numerous variations in the DNA sequences, the so-called single nucleotide polymorphisms (SNPs), affect the expression of the two genes and are relevant to different pathologies. Regulation on the RNA level includes co-transcriptional regulation like alternative splicing, as well as post-transcriptional regulation by microRNAs, long non-coding RNAs, circular RNAs, or RNA binding proteins. The review also presents a detailed characterization of the regulation of MDM2 and MDMX at the protein level, by summarizing data on numerous post-translational modifications or interacting partners of the two proteins, with regards to the different p53 contexts of the cited studies. Amongst the presented binding partners are some of the more recently identified interactors of the MDMs, which include proteins involved in the defense against several viruses. Overall, both MDM2 and MDMX stand out as extensively regulated at virtually every known level which according to the authors “attests to their relevance not only as inhibitors of p53 but of myriad other cellular activities and outcomes on their own”.
Since MDM2 and MDMX have majorly been studied in their relation to inhibit wild-type p53, of a particular interest stands a section of the review summarizing numerous processes in which the two proteins have been shown to be involved in cells lacking wild-type p53 (Figure 1).
As shown in Figure 1, the p53-independent roles of MDM2 and MDMX in cancer and in other pathologies are versatile. That hints to the importance of uncovering molecules that can modulate the deleterious effects associated with dysfunctions of the two MDMs. A summary of numerous molecules that were shown to regulate the two proteins and thus consist of potential therapeutic targets, are also discussed in the review. Again the authors put an emphasis on how such small molecules might be useful in cells that lack wild-type p53. This is important not only because the two proteins have multiple functions other than regulating wild-type p53 which can be studied in such cells, but also because an important percentage of tumors is characterized by absence of wild-type p53.
The last section of the review points out some outstanding questions and directions for future research. If the fascinating questions of the versatile p53-independent roles MDM2 and MDMX have sparked your interest, find out more from the original paper.
Brute force is usually not the best approach when trying to understand physical phenomena. Physical systems are nothing but a collection of particles. In order to study how these particles interact with each other, theorists calculate the time-evolution of the whole ensemble. As the number of particles increases, calculations become not plausible. In this context, defining clever shortcuts may be the only way to study real systems. Columbia researchers have established a new theoretical framework that calculates the conditions under which a light burst is emitted by an array of atoms – a structure used in quantum computers. They found that they can predict whether the high intensity light pulse will be emitted by looking at the first moments, thus circumventing the need of solving for the whole time evolution.
Spontaneous light emission is responsible for most of the light that we see. Examples of spontaneous emission are fireflies and the bioluminiscent bay in Puerto Rico. The physical mechanism responsible for spontaneous emission is sketched in Fig. 1a: the emitter (an atom that can be in two different energy states) is excited to a higher energy state, for example by external light. From that excited state, it spontaneously decays to a lower energy level, releasing the energy difference between the two states as a photon, i.e., as light. This is a purely quantum-mechanical process that cannot be explained by classical physics.
If multiple atoms are placed far away from each other, they act as independent units. When relaxing, they emit photons at an intensity that is proportional to the number of atoms present in the system. However, if the distance between the atoms is very small, a phenomenon called Dicke superradiance occurs.
When the atoms are very close, they interact with each other. As a result, the system as a whole cannot be regarded as the sum of many individual entities but rather as a collective system. Imagine many atoms close together forming an array, an ordered structure. External light will excite one of them, but there is no way to determine which atom within the array is the one that is excited. Effectively, all atoms are excited and not excited at the same time, the same way that Schrödinger’s cat is dead and alive at the same time. In quantum mechanics this phenomenon is called superposition. When one of the atoms relaxes, the full atomic array decays as a whole and a photon is emitted in a particular direction.
If an excited atom is isolated, there is no reason why it should emit a photon in a particular direction. However, in a coupled atomic array, constructive and destructive interference creates what are called bright and dark channels. To understand this concept, we only need a lake and a handful of rocks. When a rock is thrown into a lake, it creates a circular pattern around it by emitting a wave that travels in all the possible directions. However, if one throws many rocks close to each other into the lake, the resulting wave does not travel in all possible directions: the waves from the individual rocks interfere. Some directions will not have waves due to individual waves traveling in opposite directions (destructive interference) and the wave pattern will result from the constructive interference of the individual waves (see Fig. 1c,d). That’s exactly what happens in the atomic array: a photon – which is a quantum object and therefore can behave as a particle as well as a wave – is emitted from each atom in all possible directions, but most of those photons interfere destructively and only a few of them survive, and those constitute bright channels.
Now let’s think about the second event of photon emission. When the atoms are far away from each other, each photon would be emitted in a random direction. Nevertheless, in an atomic array, the fact that the first photon is radiated along a particular direction makes it more likely for the second photon to be radiated in that same direction. It’s like an avalanche: once the first snow has started moving down along a path, the rest of the snow follows. Once the first photon is emitted along a particular direction, the next photons follow. And that creates the superradiant burst, a high intensity pulse of light.
Theoretical calculations of superradiance in systems of many atoms are not possible due to the complexity of the calculation – the computer memory and time needed are both prohibitive. What Masson and colleagues found is that, by looking at the first two photons, one can already know if there is going to be a superradiant burst. They can anticipate if the avalanche is going to happen. This means that the early dynamics define the nature of the light emission, and a calculation of the whole time-evolution is not necessary.
Since the distance between the atoms dictates the emergence of superradiance, one may ask whether the arrangement of the atoms plays any role. Before Masson’s work, the understanding in the field was that atomic chains and rings behave differently. In an atomic chain, the two atoms at the end are different from those in the middle, since the atom at the edge has only one partner whereas the one in the middle has two. On the other hand, in a ring, all the atoms have the same environment (see Fig. 1b). And this is certainly true for a system with very few atoms. But thanks to the authors’ theoretical approach, it is now possible to include many atoms in the calculation. And they found that, despite the atoms’ arrangement, superradiance occurs equally in chains and rings when the number of atoms is very high. The reason is that, for structures with several atoms, the influence of the two placed at the end of the chain is washed out by the effect of the many atoms located in the middle. Moreover, they also found that atoms can exhibit superradiance at much larger distances than expected.
Atomic arrays are used in atomic clocks, in GPS technology, and quantum computers. In quantum technologies, each atom is used as a bit, the unit of information – it represents a 1 or a 0 depending on if it is excited or relaxed. A byte contains eight bits. As a reference, Figure 1 contains 6000000 bytes. The common belief is that interactions between the atoms and the environment produce information loss with respect to a pure, isolated system. However, Masson and Asenjo-Garcia show that interactions between the atoms results in their synchronization, producing a coherent, high intensity light burst.
When: September 21st, 1 pm-3 pm (Physics), October 19th, November 9th.
Where: Columbia University’s Zuckerman Institute (609 West 129th Street), Education Lab (ground floor).
STEM Starters is an outreach program run by Columbia University graduate students passionate about teaching STEM topics to middle and high school students. Every month, scientists and students gather together for an afternoon of experiments in different fields.
If you want to mingle and have fun while sharing your knowledge and passion with kids contact STEM Starters. For more information, check their webpage.
Volunteer with CUNO at Citizen Schools
When: Multi-visit program for this Fall semester (10 weeks).
Where: East Harlem.
CUNO (Columbia University Neuroscience Outreach) is seeking volunteers to participate in the after-school program Citizen Schools. All the lessons are already planned out and supplies are given, so except for some prep you can mostly show up and teach (or feel free to change the lessons in any way you want). A Citizen Schools teacher is there the whole time, so it ‘s an easy way to start teaching if you have no previous experience.
This semester we will be pairing with a school in East Harlem – either Renaissance School of the Arts or P.S./I.S 157 Benjamin Franklin. The class day will be determined depending on volunteer availability, with the options being Monday, Tuesday, Wednesday, or Thursday from 4:15- 5:40pm.
The first day of apprenticeships will be in the week of September 30th; the Apprenticeship Pitch Fairs will take place the week of September 16th, and theApprenticeship Design Training will be the week of September 23rd, and The WOW!s (poster session) will take place the week of December 16th.
If you think you might be interested in volunteering or have questions, please email [email protected] or [email protected]and they will get back to you with some more information!
[Please keep in mind if you decide to volunteer for this you have to commit to teaching all the sessions. If you need to miss one that is ok as long as you communicate it to the other volunteer(s) and teacher, but in general you must be available for the whole session.]
Scientist-in-Residence program is looking for passionate PhD students and postdocs to partner with New York City public school teachers to inspire the next generation of scientists. During the program Scientist-in-Residence will participate in orientation and training workshops and will develop and lead a year-long STEM project that prepares students to engage in independent research and spark their interest in STEM learning. Don’t miss this opportunity to boost your mentoring and teaching skills! The deadline to apply is July 13th.
Participants will receive a $750 stipend and $100 for travel reimbursement. For more information about the program check NYAS website or contact Program Manager Rowena Kuo ([email protected]).
The World Science festival is happening on June 2nd and the NYC chapter of SfN (braiNY) is looking for volunteers to lead neuroscience-related activities they have organized. If you want to participate sign up for a shift!
People with expertise in perception are also wanted. Bonus if you know about virtual reality. There will be a group demoing VR and some volunteers are needed to talk about the neuroscience behind it.
Feel free to contact Heather McKellar with any questions! For more information about the World Science Festival, check out their website here.
Scientific Image Contest
Do you work on the lab all day long but have a secret artistic passion? Do you feel that your neuronal stainings are a piece of art? Or do you see science in every corner of the city? Regardless of your background, here is a contest for you! Participate in the first Scientific Image Contest FotoECUSA and share your scientific art with the community. Submit your images via Twitter or Instagram before July 15th (read the complete contest rules here). For more information contact Sandra Franco.
Public Engagement Workshop
When: Thursday, August 1st – Saturday August 3rd
Where: The New York Academy of Sciences, 7 World Trade Center, 259 Greenwich St Fl 40, New York.
Are you a scientist seeking a creative outlet and connection to a broader audience? Or a creative professional who wants to inspire others with a passion for science? This 3-day workshop is for individuals interested in creating experiences that mix science with art, music and play, to introduce new audiences to the excitement of scientific discovery. Apply here!
FYI: The Office of Postdoctoral Affairs sponsors NYAS memberships for all Columbia Postdocs. So if you are not yet a member, ask Amanda Kelly.
Bridge to the Ph.D. Program aims to enhance the participation of students from underrepresented groups in STEM graduate programs. They are looking for volunteers that are willing to help scholars for their upcoming symposium, by providing feedback on their presentations. If you are interested in attending one or more of these sessions, please complete this survey. If you want more information contact Kwame Osei-Sarfo.
Volunteer at March for Science
When: May 4th
Where: Pace University, 1 Pace Plaza, New York.
Organizer of the March for Science are looking for volunteers for different activities related with the March, which will take place next May 4th.
Volunteers needed to engage in kid-friendly teach with interactive science booths and informational booths from all disciplines of STEM. The event will take place after the March ends at Pace University, 1 Pace Plaza. More info here. If you want to participate fill this out.
NYC PostDoc Coalition will have a table and anyone interested in volunteer can help at the table presenting what postdocs are, what our role in science is, how folks can help our work (support the NIH) and how younger folks can become scientists. For any interest, contact Jason Gardiner Dumelie.
Volunteer at Super Saturday STEM Expo
When: 18th May, 11am – 3pm
Where: Harlem Armory, 40 West 143rd Street
If you want to show how fun science can be, mentor young kids willing to know what is like to be a scientist and make science look as inclusive as possible volunteer for the Super Saturday STEM Expo taking place on May 18th. We are looking for people to perform hands-on activities for kids in the District of Harlem or just be there as scientists so kids can come and ask all their questions. If you are interested in participating, please contact Sandra Franco.
We’ll be doing a kite-flying activity, collecting microbes from the air! And also looking at microbes collected from kite-flying done the week before. You do not need to be a microbiology expert to help! We’re looking for volunteers to help set up, starting at 11am and then for the duration of the event. Please contact Beth Tuck from Genspace if you are available and interested. Click here for more information about the activity.
Volunteer at Family Science Night at MS 442 School of Innovation
When: Monday, May 20, 5:00-7:00pm
Where: 500 19th St, Brooklyn, NY 11215)
Volunteers will work with 6th-8th grade students and their parents on small scale, hands-on demos related to the volunteers’ work. The aims are to inspire curiosity and excitement about STEM topics and careers and to connect students and their parents with role models through in-person interactions. If you are interested, please contact Allan Powe.
Comedy training for Science Communication
Are you a minority in STEM? Are you interested in learning how to use comedy to better engage audiences? Or do you just want to become a stronger, more strategic public speaker? Apply to be part of a national cohort of supportive, intersectional science communicators with The Symposium’s free pilot training program, a supported project of Science in Vivo. More info here.