Life Sciences Commons^™

Insights Into The Molecular Roles Of Foxr2 In The Pathology Of Primary Pediatric Brain Tumors, Rajendra Gharbaran

Publications and Research

Forkhead box gene R2 (FOXR2) belongs to the family of FOX genes which codes for highly conserved transcription factors (TFs) with critical roles in biological processes ranging from development to organogenesis to metabolic and immune regulation to cellular homeostasis. A number of FOX genes are associated with cancer development and progression and poor prognosis. A growing body of evidence suggests that FOXR2 is an oncogene. Studies suggested important roles for FOXR2 in cancer cell growth, metastasis, and drug resistance. Recent studies showed that FOXR2 is overexpressed by a subset of newly identified entities of embryonal tumors. This review discusses the …

Effects Of Climate Change On Human Health, Sara El Houzaly, Richa Gupta

Publications and Research

The effects of climate change are evident worldwide as average global land and air temperatures have been rising, glaciers and ice sheets are shrinking with the concomitant rise in sea levels, extreme weather events have become more frequent, and oceans are warming and acidifying. Humanity is facing a big environmental challenge which not only impacts our habitat but will also have ramifications on our health. The present review describes a detailed examination of the scientific evidence proving the relationship between climate change and various fatal human diseases in different geographical regions. Our findings indicate that variations in the patterns of …

Incision Precision: Engaging Students During Dissection Labs, Azure N. Faucette

Publications and Research

Active learning tools, such as gamification, have facilitated teamwork and improved decision-making skills in Anatomy and Physiology classes. However, most Anatomy and Physiology labs currently contain dissection activities where students are not likely to engage in inquiry, critical thinking, or problem-solving. Usually, the instructor gives a brief lecture on the topic, and students are left to dissect without understanding how the lecture relates to what is in front of them, which is frustrating. Coupled with the frustration, some students have adverse opinions on dissecting specimens, including hesitation to dissect the specimen and religious or ethical concerns with dissection. Utilizing similar …

Females Exhibit Higher Glua2 Levels And Outperform Males In Active Place Avoidance Despite Increased Amyloid Plaques In Tgf344‑Alzheimer’S Rats, Osama Chaudry, Kelechi Ndukwe, Maria Figuiredo-Perira, Peter A. Serrano, Patricia Rockwell

Publications and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is most prevalent in females. While estrogen provides neuroprotection in females, sex mediated differences in the development of AD pathology are not fully elucidated. Therefore, comparing events between sexes in early-stage AD pathology may reveal more effective therapeutic targets of intervention. To address sex differences, we analyzed early-stage 9-month male and female TgF344-AD (Tg-AD) rats, an AD model carrying the APPswe and Presenilin 1 (PS1ΔE9) mutations that develops progressive age-dependent AD pathology similar to humans. Tg-AD females significantly outperformed Tg-AD males in the active place avoidance (aPAT) test that assesses hippocampal-dependent …

Zebras Of All Stripes Repel Biting Flies At Close Range, Kaia J. Tombak, Andrew S. Gersick, Lily V. Reisinger, Brenda Larison, Daniel I. Rubenstein

Publications and Research

The best-supported hypothesis for why zebras have stripes is that stripes repel biting flies. While this effect is well-established, the mechanism behind it remains elusive. Myriad hypotheses have been suggested, but few experiments have helped narrow the field of possible explanations. In addition, the complex visual features of real zebra pelage and the natural range of stripe widths have been largely left out of experimental designs. In paired-choice field experiments in a Kenyan savannah, we found that hungry Stomoxys flies released in an enclosure strongly preferred to land on uniform tan impala pelts over striped zebra pelts but exhibited no …

Inhibiting Glutamine Utilization Creates A Synthetic Lethality For Suppression Of Atp Citrate Lyase In Kras-Driven Cancer Cells, Ahmet Hatipoglu, Deepak Menon, Talia Levy, Maria A. Frias, David A. Foster

Publications and Research

Metabolic reprogramming is now considered a hallmark of cancer cells. KRas-driven cancer cells use glutaminolysis to generate the tricarboxylic acid cycle intermediate α -ketoglutarate via a transamination reaction between glutamate and oxaloacetate. We reported previously that exogenously supplied unsaturated fatty acids could be used to synthesize phosphatidic acid–a lipid second messenger that activates both mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTOR complex 2 (mTORC2). A key target of mTORC2 is Akt–a kinase that promotes survival and regulates cell metabolism. We report here that mono- unsaturated oleic acid stimulates the phosphoryla tion of ATP citrate lyase (ACLY) at …

A Role For Myosin Ii Clusters And Membrane Energy In Cortex Rupture For Dictyostelium Discoideum, Emmanuel Asante-Asamani, Daniel Grange, Devarshi Rawal, Zully Santiago, John Loustau, Derrick Brazill

Publications and Research

Blebs, pressure driven protrusions of the cell membrane, facilitate the movement of eukaryotic cells such as the soil amoeba Dictyostelium discoideum , white blood cells and cancer cells. Blebs initiate when the cell membrane separates from the underlying cortex. A local rupture of the cortex, has been suggested as a mechanism by which blebs are initiated. However, much clarity is still needed about how cells inherently regulate rupture of the cor- tex in locations where blebs are expected to form. In this work, we examine the role of mem- brane energy and the motor protein myosin II (myosin) in facilitating …

A Study Protocol To Prepare An Rbd Protein For Vaccine Against Covid-19, Z.M.G. Sarwar Jahangir, Arleta Helena Marnik

Publications and Research

Background: SARS-CoV-2 pandemic is a global threat to humans and the world’s economy. Effective and safe vaccines against this virus are essential to control and eradicate the pandemic. The currently applied vaccines carry SARS-CoV-2 spike-protein mRNA/cDNA. These vaccines go through several cellular processes in the recipients for producing antigens. On the contrary, the SARS-CoV-2 RBD (receptor binding domain)-protein is an antigen. It will directly stimulate antibody production against SARS-CoV-2. Hence, we propose to produce SARS-CoV-2 RBD-protein as a fast acting, effective and safe vaccine.

Methods: We propose to reconstruct a plasmid carrying three types of DNA sequences: RBD cDNA, FP …

Importin-Mediated Pathological Tau Nuclear Translocation Causes Disruption Of The Nuclear Lamina, Tdp-43 Mislocalization And Cell Death, Robert F. Candia, Leah S. Cohen, Viktoriya Morozova, Christopher Corbo, Alejandra D. Alonso

Publications and Research

Tau is a cytosolic protein that has also been observed in the nucleus, where it has multiple proposed functions that are regulated by phosphorylation. However, the mechanism underlying the nuclear import of tau is unclear, as is the contribution of nuclear tau to the pathology of tauopathies. We have previously generated a pathological form of tau, PH-tau (pseudophosphorylation mutants S199E, T212E, T231E, and S262E) that mimics AD pathological behavior in cells, Drosophila, and a mouse model. Here, we demonstrated that PH-tau translocates into the nucleus of transiently transfected HEK-293 cells, but wildtype tau does not. We identified a putative …

Exploration Of Dark Chemical Genomics Space Via Portal Learning: Applied To Targeting The Undruggable Genome And Covid-19 Anti-Infective Polypharmacology, Tian Cai, Li Xie, Muge Chen, Yang Liu, Di He, Shuo Zhang, Cameron Mura, Philip Boume, Lei Xie

Publications and Research

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning , to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) …

A New Function For Amyloid-Like Interactions: Cross-Beta Aggregates Of Adhesins Form Cell-To-Cell Bonds, Peter N. Lipke, Marion Mathelié-Guinlet, Albertus Viljoen, Yves F. Dufrêne

Publications and Research

Amyloid structures assemble through a repeating type of bonding called “cross-β”, in which identical sequences in many protein molecules form β-sheets that interdigitate through side chain interactions. We review the structural characteristics of such bonds. Single cell force microscopy (SCFM) shows that yeast expressing Als5 adhesin from Candida albicans demonstrate the empirical characteristics of cross-β interactions. These properties include affinity for amyloid-binding dyes, birefringence, critical concentration dependence, repeating structure, and inhibition by anti-amyloid agents. We present a model for how cross-β bonds form in trans between two adhering cells. These characteristics also apply to other fungal adhesins, so the mechanism …

Development Of An Online General Biology Open Educational Resource (Oer) Laboratory Manual, Dmitry Y. Brogun, Azure N. Faucette, Kristin Polizzotto, Farshad Tamari

Publications and Research

Currently, many academic institutions are using one or more variations of online modalities due to the COVID-19 pandemic, and science educators face a unique challenge with distance-learning laboratories. Many resources to engage students in virtual, interactive laboratory activities exist, but we found that high costs and/or overlooked content left gaps for several topics typically taught in a general, introductory biology course for undergraduate biology majors (e.g., organismal biology). Additionally, resources for an online lab must be identified and curated from multiple sources, requiring intense demands on the instructors’ time. To meet this need and to overcome the financial burden of …

A Review Of Sars-Cov-2, Responsible For Covid-19: History, Biology, Infection Mechanism, Antigenic Vaccines, Their Risks And How An Alternate Rbd Vaccine Is Safer?, Zmg Sarwar Jahangir, Arleta Helena Marnik

Publications and Research

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some …

Maternal Cannabis Use Is Associated With Suppression Of Immune Gene Networks In Placenta And Increased Anxiety Phenotypes In Offspring, Gregory Rompala, Yoko Nomura, Yasmin L. Hurd

Publications and Research

While cannabis is among the most used recreational drugs during pregnancy, the impact of maternal cannabis use (mCB) on fetal and child development remains unclear. Here, we assessed the effects of mCB on psychosocial and physiological measures in young children along with the potential relevance of the in-utero environment reflected in the placental transcriptome. Children (~3-6 years) were assessed for hair hormone levels, neurobehavioral traits on the behavioral assessment system for children (BASC-2) survey, and heart rate variability (HRV) at rest and during auditory startle. For a subset of children with behavioral assessments, placental specimens collected at birth were processed …

Immunohistochemical Localization Of Prolactin Receptor (Prlr) To Hodgkin's And Reed-Sternberg Cells Of Hodgkin's Lymphoma, Rajendra Gharbaran, Onyekwere Onwumere, Naomi Codrington, Latchman Somenarian, Stephen Redenti

Publications and Research

Prolactin receptor (PRLR), a type-1 cytokine receptor, is overexpressed in a number of cancer types. It has attracted much attention for putative pro-oncogenic roles, which however, remains controversial in some malignancies. In this study, we reported the localization of PRLR to the Hodgkin's and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL), a neoplasm of predominantly B cell origin. Immunohistochemistry performed on 5-μm thick FFPE sections revealed expression of PRLR in HRS cells. Cellular immunofluorescence experiments showed that the HL-derived cell lines, Hs445, KMH2 and L428 overexpressed PRLR. The PRLR immunofluorescent signal was depleted after treating the cell lines with 10 …

A Multi‑Disciplinary Comparison Of Great Ape Gut Microbiota In A Central African Forest And European Zoo, Victor Narat, Katherine R. Amato, Noémie Ranger, Maud Salmona, Séverine Mercier‑Delarue, Stephanie Rupp, Philippe Ambata, Richard Njouom, François Simon, Tamara Giles‑Vernick, Jérôme Legoff

Publications and Research

Comparisons of mammalian gut microbiota across different environmental conditions shed light on the diversity and composition of gut bacteriome and suggest consequences for human and animal health. Gut bacteriome comparisons across different environments diverge in their results, showing no generalizable patterns linking habitat and dietary degradation with bacterial diversity. The challenge in drawing general conclusions from such studies lies in the broad terms describing diverse habitats (“wild”, “captive”, “pristine”). We conducted 16S ribosomal RNA gene sequencing to characterize intestinal microbiota of free-ranging sympatric chimpanzees and gorillas in southeastern Cameroon and sympatric chimpanzees and gorillas in a European zoo. We conducted …

Hypogean Communities As Cybernetic Systems: Implications For The Evolution Of Cave Biotas, Aldemaro Romero Jr.

Publications and Research

Ramón Margalef proposed in 1968 that ecosystems could be better understood if they were viewed as cybernetic systems. I tested this hypothesis in the case of hypogean ecosystems using available pieces of evidence. I looked on how information on feedbacks, stability, succession, organization, diversity, and energy flows in the hypogean environment fit the cybernetics hypothesis. The results were that there are convincing arguments that the application of the concept of cybernetics in biospeleology can be beneficial to broadening our understanding of cave biota in terms of their structure. I also make the case that this approach can provide more clarity …

Luteolin Induces Cytotoxicity In Mix Cellularity Classical Hodgkin's Lymphoma Via Caspase Activated-Cell Death, Rajendra Gharbaran, Enyuan Shang, Onyekwere Onwumere, Naomi Codrington, Evangelina Dankwa Sarpong, Stephen M. Redenti

Publications and Research

Background/aim: We investigated the effects of luteolin (LUT) on classical Hodgkin's lymphoma (cHL), since such studies in malignant lymphomas are lacking.

Materials and methods: Effect of LUT on cell growth was assessed with water-soluble tetrazolium 1 (WST-1) cell proliferation assay and automated hemocytometry on trypan blue-exclusion assay. Cell death was investigated with acridine orange/ethidium bromide live-dead assay, propidium iodide (PI) flow cytometry, and Annexin-V-PI microscopy. Caspase activation was studied using CellEvent Caspase-3/7 Green detection reagent. High resolution immunofluorescence microscopy was used to detect cleaved-PARP-1.

Results: LUT induced a dose-dependent decrease in the growth of KMH2 and L428 cells, cellular models …

Identification Of Tandem Repeat Families From Long-Read Sequences Of Humulus Lupulus, Katherine A. Easterling, Nicholi J. Pitra, Taylan B. Morcol, Jenna R. Aquino, Lauren G. Lopes, Kristin C. Bussey, Paul D. Matthews, Hank W. Bass

Publications and Research

Hop (Humulus lupulus L.) is known for its use as a bittering agent in beer and has a rich history of cultivation, beginning in Europe and now spanning the globe. There are five wild varieties worldwide, which may have been introgressed with cultivated varieties. As a dioecious species, its obligate outcrossing, non-Mendelian inheritance, and genomic structural variability have confounded directed breeding efforts. Consequently, understanding the hop genome represents a considerable challenge, requiring additional resources. In order to facilitate investigations into the transmission genetics of hop, we report here a tandem repeat discovery pipeline developed using k-mer filtering and dot plot …

Taking A Closer Look On The Coronavirus, Alisha Barday, Janina Duran, Lisa Agranov

Publications and Research

No abstract provided.

Cov Genome Tracker: Tracing Genomic Footprints Of Covid-19 Pandemic, Saymon Akther, Edgaras Bezrucenkovas, Brian Sulkow, Christopher Panlasigui, Li Li, Wei-Gang Qiu, Lia Di

Publications and Research

Genome sequences constitute the primary evidence on the origin and spread of the 2019-2020 Covid-19 pandemic. Rapid comparative analysis of coronavirus SARS-CoV-2 genomes is critical for disease control, outbreak forecasting, and developing clinical interventions. CoV Genome Tracker is a web portal dedicated to trace Covid-19 outbreaks in real time using a haplotype network, an accurate and scalable representation of genomic changes in a rapidly evolving population. We resolve the direction of mutations by using a bat-associated genome as outgroup. At a broader evolutionary time scale, a companion browser provides gene-by-gene and codon-by-codon evolutionary rates to facilitate the search for molecular …

C-Di-Gmp Modulates Type Iv Msha Pilus Retraction And Surface Attachment In Vibrio Cholerae, Kyle A. Floyd, Calvin K. Lee, Wujing Xian, Mahmoud Nametalla, Aneesa Valentine, Benjamin Crair, Shiwei Zhu, Hannah Q. Hughes, Jennifer L. Chlebek, Daniel C. Wu, Jin Hwan Park, Ali M. Farhat, Charles J. Lomba, Courtney K. Ellison, Yves V. Brun, Javier Campos-Gomez, Ankur B. Dalia, Jun Liu, Nicolas Biais, Gerard C. L. Wong, Fitnat H. Yildiz

Publications and Research

Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3’,5’-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retrac- tion. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attach- ment results …

Predictor Species: Improving Assessments Of Rare Species Occurrence By Modeling Environmental Co-Responses, Peter R. Thompson, William F. Fagan, Phillip P. A. Staniczenko

Publications and Research

Designing an effective conservation strategy requires understanding where rare species are located. Because rare species can be difficult to find, ecologists often identify other species called conservation surrogates that can help inform the distribution of rare species. Species distribution models typically rely on environmental data when predicting the occurrence of species, neglecting the effect of species' co-occurrences and biotic interactions. Here, we present a new approach that uses Bayesian networks to improve predictions by modeling environmental co-responses among species. For species from a European peat bog community, our approach consistently performs better than single-species models and better than conventional multi-species …

Transposon Mutagenesis In Mycobacterium Kansasii Links A Small Rna Gene To Colony Morphology And Biofilm Formation And Identifies 9,885 Intragenic Insertions That Do Not Compromise Colony Outgrowth, William C. Budell, Gabrielle A. Germain, Niklas Janisch, Zaid Mckie-Krisberg, Anitha D. Jayaprakash, Andrew E. Resnick, Luis E. N. Quadri

Publications and Research

Mycobacterium kansasii (Mk) is a resilient opportunistic human pathogen that causes tuberculosis-like chronic pulmonary disease and mortality stemming from comorbidities and treatment failure. The standard treatment of Mk infections requires costly, long-term, multidrug courses with adverse side effects. The emergence of drug-resistant isolates further complicates the already challenging drug therapy regimens and threatens to compromise the future control of Mk infections. Despite the increasingly recognized global burden of Mk infections, the biology of this opportunistic pathogen remains essentially unexplored. In particular, studies reporting gene function or generation of defined mutants are scarce. Moreover, no transposon (Tn) mutagenesis tool has been …

Exploring The Potential Of Nitric Oxide And Hydrogen Sulfide (Nosh)-Releasing Synthetic Compounds As Novel Priming Agents Against Drought Stress In Medicago Sativa Plants, Chrystalla Antoniou, Rafaella Xenofontos, Giannis Chatzimichail, Anastasis Christou, Khosrow Kashfi, Vasileios Fotopoulos

Publications and Research

Land plants are continuously exposed to multiple abiotic stress factors like drought, heat, and salinity. Nitric oxide (NO) and hydrogen sulfide (H2S) are two well-examined signaling molecules that act as priming agents, regulating the response of plants to stressful conditions. Several chemical donors exist that provide plants with NO and H2S separately. NOSH is a remarkable novel donor as it can donate NO and H2S simultaneously to plants, while NOSH-aspirin additionally provides the pharmaceutical molecule acetylsalicylic acid. The current study aimed to investigate the potential synergistic effect of these molecules in drought-stressed Medicago sativa L. plants by following a pharmacological …

Water In Your Neighbourhood: A Model For Implementing A Semester-Long Course-Based Undergraduate Research Project In Introductory Biology, Ana Lucia Fuentes, Maria Entezari

Publications and Research

Undergraduate biology education has changed over the past decade, incorporating an iterative and evidence-based approach. Many educational assessments have confirmed the effectiveness of integrating authentic research and open-ended inquiry into introductory biology courses, demonstrating a significant positive impact on students’ learning and attitude towards STEM majors. Despite these findings, only a handful of Biology instructors in 2-year colleges adopt this approach, and when adopted, most activities constitute a small fraction of these courses. Finding a feasible, sustainable, semester-long, and cost-effective strategy to incorporate authentic research in the curriculum which promotes integrated understanding of science and addresses socio-scientific issues, is a …

Sediment Microbiomes Associated With Critical Habitat Of The Juvenile American Horseshoe Crab; Limulus Polyphemus, J. Petersen, Christina P. Colon, J. L. Joyner

Publications and Research

Plumb Beach, Brooklyn, New York in USA is an important horseshoe crab breeding and nursery ground that has experienced substantial anthropogenic influence, including pollution, erosion and subsequent restoration. Since little is known about the relationship between sediment microbial communities and juvenile horseshoe crab survival, next generation sequencing was used to characterize and compare the sediment microbiome of three distinct areas of Plumb Beach:- a tidal creek with abundant juveniles, East Beach with moderate number of juveniles, and West Beach- a highly disturbed area where juvenile crabs are rarely seen. The microbiome of juvenile crab intestinal content (both dissected gut content …

Venom Diversity And Evolution In The Most Divergent Cone Snail Genus Profundiconus, Guilia Fassio, Maria Vittoria Modica, Lou Mary, Paul Zaharias, Alexander E. Fedosov, Juliette Gorson, Yuri I. Kantor, Mandë E. Holford, Nicolas Puillandre

Publications and Research

Profundiconus is the most divergent cone snail genus and its unique phylogenetic position, sister to the rest of the family Conidae, makes it a key taxon for examining venom evolution and diversity. Venom gland and foot transcriptomes of Profundiconus cf. vaubani and Profundiconus neocaledonicus were de novo assembled, annotated, and analyzed for differential expression. One hundred and thirty-seven venom components were identified from P. cf. vaubani and 82 from P. neocaledonicus, with only four shared by both species. The majority of the transcript diversity was composed of putative peptides, including conotoxins, profunditoxins, turripeptides, insulin, and prohormone-4. However, there were also …

Invertebrate Retinal Progenitors As Regenerative Models In A Microfluidic System, Caroline D. Pena, Stephanie Zhang, Robert Majeska, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insuffcient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to …

An Amyloid Core Sequence In The Major Candida Albicans Adhesin Als1p Mediates Cell-Cell Adhesion, Vida Ho, Philippe Herman-Bausier, Christopher Shaw, Karen A. Conrad, Melissa C. Garcia-Sherman, Jeremy Draghi, Yves F. Dufrene, Peter N. Lipke, Jason M. Rauceo

Publications and Research

ABSTRACT The human fungal commensal Candida albicans can become a serious opportunistic pathogen in immunocompromised hosts. The C. albicans cell adhesion protein Als1p is a highly expressed member of a large family of paralogous adhesins. Als1p can mediate binding to epithelial and endothelial cells, is upregulated in infections, and is important for biofilm formation. Als1p includes an amyloidforming sequence at amino acids 325 to 331, identical to the sequence in the paralogs Als5p and Als3p. Therefore, we mutated Val326 to test whether this sequence is important for activity. Wild-type Als1p (Als1pWT) and Als1p with the V326N mutation (Als1pV326N) were expressed …