The rockefeller university

Affecting basic tenets of human existence such as health, economic as well as personal security and, of course, reproduction, the COVID-19 pandemic transcended medical specialties and professional disciplines. Yet, six months into the pandemic, there still exists no consensus on how to combat the virus in absence of a vaccine. Facing unprecedented circumstances, and in absence of real evidence on how to proceed, our organization early in the pandemic decided to act independently from often seemingly irrational guidance and, instead, to carefully follow a quickly evolving COVID-19 literature. Here described is the, likely, unique journey of a fertility center that maintained services during peaks of COVID-19 and political unrest that followed. Closely following publicly available data, we recognized relatively early that New York City and other East Coast regions, which during the initial COVID-19 wave between March and May represented the hardest-hit areas in the country, during the second wave, beginning in June and still in progress, remained almost completely unaffected. In contrast, south western regions, almost completely unaffected by the initial wave, were severely affected in the second wave. These two distinctively different infectious phenotypes suggested two likely explanations: The country was witnessing infections with two different SARS-CoV-2 viruses and NYC (along with the East Coast) acquired during the first wave much better immunity to the virus than south western regions. Both hypotheses since have been confirmed: East and West Coasts, indeed, were initially infected by two distinctively different lineages of the virus, with the East Coast lineage being 10-times more infectious. In addition, immunologists discovered an up to this point unknown long-term anti-viral innate (cellular) immune response which offers additional and much broader anti-viral immunity than the classical adaptive immunity via immobilizing antibodies that has been known for decades. Consequently, we predict that in the U.S., even in absence of an available vaccine, COVID-19, by September-October, will be at similarly low levels as are currently seen in NYC and other East Coast regions (generally < 1% test-positivity). We, furthermore, predict that, if current mitigation measures are maintained and no newly aggressive mutation of the virus enters the country, a significant fall-wave of COVID-19, in combination with the usual fall wave of influenza, appears unlikely. To continue serving patients uninterrupted throughout the pandemic, turned for all of our center's staff into a highly rewarding experience, garnered respect and appreciation from patients, and turned into an absolutely unique learning experience.

Gene and cell therapy products approved over the past decade in Europe and North America have provided new therapeutic options for single gene disorders and for hematologic malignancies. Lessons learned, and limitations identified, are reviewed.

Recent years have seen a surge in methods to track and analyze animal behavior. Nevertheless, tracking individuals in closely interacting, group-living organisms remains a challenge. Here, we present anTraX, an algorithm and software package for high-throughput video tracking of color-tagged insects. anTraX combines neural network classification of animals with a novel approach for representing tracking data as a graph, enabling individual tracking even in cases where it is difficult to segment animals from one another, or where tags are obscured. The use of color tags, a well-established and robust method for marking individual insects in groups, relaxes requirements for image size and quality, and makes the software broadly applicable. anTraX is readily integrated into existing tools and methods for automated image analysis of behavior to further augment its output. anTraX can handle large-scale experiments with minimal human involvement, allowing researchers to simultaneously monitor many social groups over long time periods.

Interactions between microbial symbionts influence their demography and that of their hosts. Taylor's power law (TL)-a well-established relationship between population size mean and variance across space and time-may help to unveil the factors and processes that determine symbiont multiplications. Recent studies suggest pervasive interactions between symbionts in Drosophila melanogaster. We used this system to investigate theoretical predictions regarding the effects of interspecific interactions on TL parameters. We assayed twenty natural strains of bacteria in the presence and absence of a strain of yeast using an ecologically realistic set-up with D. melanogaster larvae reared in natural fruit. Yeast presence led to a small increase in bacterial cell numbers; bacterial strain identity largely affected yeast multiplication. The spatial version of TL held among bacterial and yeast populations with slopes of 2. However, contrary to theoretical prediction, the facilitation of bacterial symbionts by yeast had no detectable effect on TL's parameters. These results shed new light on the nature of D. melanogaster's symbiosis with yeast and bacteria. They further reveal the complexity of investigating TL with microorganisms.

Immunological memory is required for protection against repeated infections and is the basis of all effective vaccines. Antibodies produced by memory B cells play an essential role in many of these responses. We have combined lineage tracing with antibody cloning from single B cells to examine the role of affinity in B cell selection into germinal centers (GCs) and the memory B cell compartment in mice immunized with an HIV-1 antigen. We find that contemporaneously developing memory and GC B cells differ in their affinity for antigen throughout the immune response. Whereas GC cells and their precursors are enriched in antigen binding, memory B cells are not. Thus, the polyclonal memory B cell compartment is composed of B cells that were activated during the immune response but whose antigen binding affinity failed to support further clonal expansion in the GC.

The synthesis of ATP, life's "universal energy currency," is the most prevalent chemical reaction in biological systems and is responsible for fueling nearly all cellular processes, from nerve impulse propagation to DNA synthesis. ATP synthases, the family of enzymes that carry out this endless task, are nearly as ubiquitous as the energy-laden molecule they are responsible for making. The F-type ATP synthase (F-ATPase) is found in every domain of life and has facilitated the survival of organisms in a wide range of habitats, ranging from the deep-sea thermal vents to the human intestine. Accordingly, there has been a large amount of work dedicated toward understanding the structural and functional details of ATP synthases in a wide range of species. Less attention, however, has been paid toward integrating these advances in ATP synthase molecular biology within the context of its evolutionary history. In this review, we present an overview of several structural and functional features of the F-type ATPases that vary across taxa and are purported to be adaptive or otherwise evolutionarily significant: ion channel selectivity, rotor ring size and stoichiometry, ATPase dimeric structure and localization in the mitochondrial inner membrane, and interactions with membrane lipids. We emphasize the importance of studying these features within the context of the enzyme's particular lipid environment. Just as the interactions between an organism and its physical environment shape its evolutionary trajectory, ATPases are impacted by the membranes within which they reside. We argue that a comprehensive understanding of the structure, function, and evolution of membrane proteins-including ATP synthase-requires such an integrative approach.

Following oxycodone (Oxy) conditioned place preference (CPP), delta opioid receptors (DORs) differentially redistribute in hippocampal CA3 pyramidal cells in female and male rats in a manner that would promote plasticity and opioid-associative learning processes. However, following chronic immobilization stress (CIS), males do not acquire Oxy-CPP and the trafficking of DORs in CA3 pyramidal neurons is attenuated. Here, we examined the subcellular distribution of DORs in CA1 pyramidal cells using electron microscopy in these same cohorts. CPP: Saline (Sal)-females compared to Sal-males have more cytoplasmic and total DORs in dendrites and more DOR-labeled spines. Following Oxy-CPP, DORs redistribute from near-plasmalemma pools in dendrites to spines in males. CIS: Control females compared to control males have more near-plasmalemmal dendritic DORs. Following CIS, dendritic DORs are elevated in the cytoplasm in females and near-plasmalemma in males. CIS plus CPP: CIS Sal-females compared to CIS Sal-males have more DORs on the plasmalemma of dendrites and in spines. After Oxy, the distribution of DORs does not change in either females or males. Conclusion: Following Oxy-CPP, DORs within CA1 pyramidal cells remain positioned in naive female rats to enhance sensitivity to DOR agonists and traffic to dendritic spines in naive males where they can promote plasticity processes. Following CIS plus behavioral enrichment, DORs are redistributed within CA1 pyramidal cells in females in a manner that could enhance sensitivity to DOR agonists. Conversely, CIS plus behavioral enrichment does not alter DORs in CA1 pyramidal cells in males, which may contribute to their diminished capacity to acquire Oxy-CPP.

Polarized growth requires the integration of polarity pathways with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake. In budding yeast, the myosin-V Myo2 is aided by the kinesin-related protein Smy1 in carrying out the essential Sec4-dependent transport of secretory vesicles to sites of polarized growth. Overexpression suppressors of a conditional myo2 smy1 mutant identified a novel F-BAR (Fes/CIP4 homology-Bin-Amphiphysin-Rvs protein)-containing RhoGAP, Rgd3, that has activity primarily on Rho3, but also Cdc42. Internally tagged Rho3 is restricted to the plasma membrane in a gradient corresponding to cell polarity that is altered upon Rgd3 overexpression. Rgd3 itself is localized to dynamic polarized vesicles that, while distinct from constitutive secretory vesicles, are dependent on actin and Myo2 function. In vitro Rgd3 associates with liposomes in a PIP2-enhanced manner. Further, the Rgd3 C-terminal region contains several phosphorylatable residues within a reported SH3-binding motif. An unphosphorylated mimetic construct is active and highly polarized, while the phospho-mimetic form is not. Rgd3 is capable of activating Myo2, dependent on its phospho state, and Rgd3 overexpression rescues aberrant Rho3 localization and cell morphologies seen at the restrictive temperature in the myo2 smy1 mutant. We propose a model where Rgd3 functions to modulate and maintain Rho3 polarity during growth.

New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies(1-3). For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database(4) increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies(5) are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus(6), a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far. The Progressive Cactus program can create reference-free alignments of hundreds of large vertebrate genomes efficiently, and is used for the alignment of more than 600 amniote genomes.

The advance of science is dependent upon collaboration, which does not have a visa attached to it. Indeed, over 40% of all American-based Nobel Prize winners are immigrants, and data from the National Science Foundation show that 49% of postdocs and 29% of science and engineering faculty in the US are foreign-born. However, restrictive new immigration policies in the US have left many scientists deeply concerned about their future and many American-based laboratories worried about attracting the best talent. At JEM, we're celebrating immigration by sharing the experiences of immigrant and nonimmigrant scientists on our editorial board. Alexander Rudensky and Jean-Laurent Casanova give their firsthand perspective on immigrating to the US, while JeddWolchok, Carl Nathan, David Holtzman, Susan Kaech, Lewis Lanier, and David Tuveson reflect on how immigration has affected their laboratories.