Biology subjects

Miller, K. B.

Publications and source records attributed to Miller, K. B..

7 recordsLinked to original sources

bioRxiv2026

NM-RARe: A FRAMEWORK FOR REGIONAL ARTHROPOD CONSERVATION ASSESSMENT: INSIGHTS FROM NEW MEXICO

Arthropods represent the most species-rich animal group on the planet, yet they remain largely overlooked in formal conservation planning. New Mexico is a US state with exceptional biodiversity, including numerous endemic, rare, and threatened arthropod species. Recent attention to global insect declines has highlighted the need to document possible threats to and declines of New Mexico insects and other arthropods. All terrestrial arthropods in New Mexico lacked state-level regulatory protection until 2025, and baseline data on the taxonomy, ecology, geographic distribution and conservation needs for most New Mexico arthropod species remained absent. To address this gap, we developed the New Mexico Rare Arthropod Resource (NM-RARe), a publicly accessible regional database for arthropod species and subspecies of conservation concern in New Mexico. Drawing from multiple vetted sources, we compiled an initial working list of 7,018 taxa and conducted 261 preliminary IUCN Red List assessments and 185 NatureServe state rank assessments, covering 285 total taxa. Of those assessed by IUCN Red List standards, 52 were subspecies and 209 were species level assessments, 165 of which met the criteria for inclusion and were incorporated into the NM-RARe database (https://nmrare.org/). Ninety-three of the pollinating insect species from NM-RARe were then formally incorporated into New Mexico's 2025 State Wildlife Action Plan (SWAP), representing a significant conservation milestone. Beyond its immediate regional impact, NM-RARe presents a standardized, scalable methodology adaptable to any region or taxonomic group, offering a replicable framework for arthropod conservation assessment worldwide.

ecology↗

bioRxiv2026

Reward-tethered place cells support flexible magnitude coding and remapping in the hippocampus

Learning to navigate a changing environment requires the ability to detect when a reward no longer matches a previous expectation. While the hippocampus is essential for adapting behavior strategies when reward expectations are violated and is known to integrate goal-related information into spatial maps, the precise dynamics by which these maps update during an unexpected reduction in reward magnitude is not well understood. Using longitudinal calcium imaging of neuronal activity in behaving mice, we found that hippocampal CA1 population activity encodes reward magnitude through elevated event rates at high value locations. Within this population, we discovered a specialized group of reward tethered place cells that bind spatial context to reward magnitude. These reward tethered place cells exhibit spatial fields across the environment while simultaneously exhibiting activity anchored to high-value reward locations. Upon reward reduction, CA1 population activity equalizes and these neurons undergo a selective and rapid remapping that precedes behavioral adjustment to the reward downshift. The broader spatial map remains intact, indicating that this change allows the animal to update the value of a goal while preserving a stable representation of its surroundings. This selective reorganization of hippocampal firing patterns could support adaptive decision making by updating internal models of the world when expectations are violated. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/725501v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@1725be8org.highwire.dtl.DTLVardef@eff7c1org.highwire.dtl.DTLVardef@72d4b3org.highwire.dtl.DTLVardef@ea3e41_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract.C_FLOATNO Masala N., Donahue M., etal. C_FIG

neuroscience↗

bioRxiv2025

Rediscovery and ecology of the Capulin Mountain Alberta arctic butterfly: informing data collection for rare endemics

Insect conservation in the southwestern United States is hindered by limited information on distribution, phenology, and habitat, especially for small-range endemics. The Capulin Mountain Alberta Arctic butterfly (Oeneis alberta capulinensis F.M. Brown, 1970), a New Mexico Species of Greatest Conservation Need, is restricted to the Raton Mesa Complex and threatened by isolation, low dispersal, and extirpation from its type locality. We surveyed historic and potential sites to document current distribution, refine flight phenology, investigate larval host plant use, and assess habitat condition. Our results confirm extant populations, identify the larval host plant (Festuca idahoensis Elmer), and describe habitat as montane grasslands with limited woody encroachment. A habitat suitability model predicted additional potentially occupied areas, highlighting under-explored habitat for future monitoring. This study provides the first comprehensive ecological assessment of O. a. capulinensis and establishes a framework for documenting poorly known endemic insects to guide future research and survey design.

ecology↗

bioRxiv2022

Follicular helper T cells expressing Blimp1 are specialized for plasma cell differentiation

B cells differentiate into antibody-producing plasma cells (PC) and germinal center (GC) B cells under the guidance of specialized CD4+ follicular helper T (TFH) cells. Here, we demonstrate that CD4 T cells require Prdm1 expression for both early PC differentiation and post-GC PC formation. Using dual Blimp1/Foxp3 reporter mice and single cell-indexed analysis, we segregate persistent compartments and expressed transcriptional programs of Blimp1+ CXCR5+PD1hi TFH (referred to here as PC-TFH) from canonical Blimp1- Bcl6+ TFH (GC-TFH) and Blimp1+Foxp3+ TFR immune regulators. Antigen recall expands localized PC-TFH compartments with rapidly divergent antigen-specific memory PC-TFH and GC-TFH programs. Thus, Blimp1 is a central mediator of PC-TFH function producing specialized TFH subsets that co-ordinate with GC-TFH function to establish high-affinity long-lasting protective immunity to vaccines and infection. One-Sentence SummaryBlimp1 expressing TFH cells express unique transcriptional programs to control PC formation RESEARCH ARTICLE SUMMARYO_ST_ABSIntroductionC_ST_ABSAdaptive B cell immunity rapidly emerges to form plasma cells (PC) for antibody production and non-PC that enter germinal centers (GC) to evolve higher affinity B cell receptors. Both pathways are essential to long-term high-affinity immune protection. The early PC to GC cell fate division is driven by B cell expression of mutually antagonist transcriptional repressors Blimp1 and Bcl6. This dichotomous B cell outcome is orchestrated through antigen-specific contact by follicular helper T (TFH) cells that express Bcl6 to upregulate CXCR5, localize into B cell regions and express transcriptional programs that influence B cell fate and function. It remains unclear what TFH cell mechanisms differentially impact these divergent B cell pathways. RationaleBlimp1 is found in Foxp3+ follicular regulatory T (TFR) cells known to impact GC B cell outcomes and play a role controlling antibody-mediated autoimmunity. In the context of infection, induced Blimp1 expression in CD4 T cells is expressed by conventional non-TFH effector cell compartments. Blimp1 segregates with emigrant CD4 T cells that leave the reactive lymphoid tissue to control innate immune function at the site of antigen entry. Conversely, Bcl6 is predominantly expressed in the GC regulating TFH pathway and is demonstrated to suppress Blimp1 expression. Germline ablation of Bcl6 exaggerates type 2 effector TH cell functions that promote excessive antibody production in the absence of the GC reaction. Similarly, loss of Bcl6 in CD4 T cells abrogates GC formation and post-GC PC responses, however multiple recent reports indicate continued support for antibody production without a Bcl6+ TFH compartment. To reconcile these findings, we propose a division of TFH function with separable pathways to regulate PC and GC differentiation. We hypothesize a central role for persistent CD4 T cell expressed Blimp1 that segregates early TFH transcriptional control to create an effector cell program that selectively targets PC differentiation. ResultsDirect intracellular staining for protein, confirmed with single Blimp1 and dual (Foxp3) reporter mice, identified Blimp1 expressing CXCR5+PD1hi TFH and TFR subsets within the spleen, bone marrow and other lymphoid tissues at steady-state. Conditional deletion of Prdm1 in CD4 T cells and adoptive transfer into immunodeficient hosts with splenic B cells, truncated both early pre-GC and late post-GC formation of PC providing a causal link to both pathways of differentiation in vivo. Across steady-state splenic T cells, in vitro activated Blimp1+CD25- CD4 T cells in T-B cell co-cultures correlated with significant levels of PC induction. Integrated single cell-indexed strategies segregate the transcriptional programs of Blimp1 expressing TFH cells (referred to here as PC-TFH) from canonical GC-inducing Bcl6+ TFH cells (GC-TFH), both distinct from Blimp1+ TFR cell programs in the steady-state. Immunization and recall produce follicular localized PC-TFH with pMHCII-tetramer binding memory response TFH cells that segregate across PC-TFH and GC-TFH compartments re-iterating the dichotomous transcriptome seen at steady-state. ConclusionThis study identifies Blimp1 as a key mediator of PC-TFH cells that sub-specialize as inducers of PC differentiation and bifurcate from the Bcl6+ GC-TFH cell pathway and functions. Persistent PC-TFH compartments assort across multiple lymphoid tissues at steady-state and are distinct from Foxp3+Blimp1+ TFR immune regulators. While PC TFH cells alone are required for early and rapid antibody responses, both TFH sub-classes are essential to the generation of high-affinity long-lived and memory response PC compartments. Cellular organization and molecular components of the PC-TFH transcriptional program indicate functional sub-specialization that can be separately targeted for immunotherapeutic purposes and adjuvant design in future vaccines. Sub-specialized Blimp1+ PC-TFH cells control PC differentiationAdaptive immune protection requires balancing the evolution of BCR affinity within germinal center (GC) B cells and the differentiation of plasma cells (PC) for production of antibodies. Both functional B cell pathways require the antigen-specific induction of specialized CD4+ follicular T (TFH) cells. Within GC-inducing TFH cells, Bcl6 is required to drive the formation and function of GC B cells. Here, we segregate PC-inducing TFH cells that require Blimp1 as a key mediator of antigen-specific PC differentiation. The Blimp1+ PC-TFH transcriptional program diverges from Bcl6+ GC-TFH compartment and Blimp1+Foxp3+ follicular regulatory T (TFR) compartments. Antigen-specific PC-TFH emerge and segregate rapidly from GC-TFH after priming and recall to co-operatively induce effective long-term adaptive immunity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/486642v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@b96936org.highwire.dtl.DTLVardef@aa8be3org.highwire.dtl.DTLVardef@c6095aorg.highwire.dtl.DTLVardef@1900ec7_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

PD-1 checkpoint blockade activates germinal center follicular T cell programs that disrupt type 2 isotype-specific antibody homeostasis

Multiple CD4 T cell dependent tolerance mechanisms control adaptive B cell immunity to environmental antigens. We recently demonstrated a PD-1 checkpoint within steady-state splenic germinal centers (GC) that constrains the maturation of type 2 IgG1 isotype-specific antibody homeostasis. Here, we utilized single cell-indexed custom RNA-sequencing to probe the follicular T cell mechanisms directly targeted by acute PD-1 blockade. We find a pre-existing subset of follicular helper T (TFH) cells that express type 2 immune response properties (TFH2) with exaggerated pathways of TCR activation, cytokine signaling, and enhanced cell-cell contact upon acute PD-1 blockade. This selective amplification of the TFH2 program significantly increases predicted molecular connections to type 2 IgG1 GC B cells that dominate limited changes in GC localized follicular regulatory T (GC TFR) cell programs. These studies demonstrate how type 2 isotype-specific adaptive B cell tolerance is selectively disrupted by acute PD-1 blockade to reveal the modular regulatory mechanisms that control splenic GC dynamics at homeostasis. One Sentence SummaryAcute PD-1 blockade alters the regulatory dynamic of the steady state germinal center to drive the maturation of IgG1 GC B cells towards PC differentiation in a process mediated by type 2 like TFH effector molecules. HIGHLIGHTS- Acute PD-1 blockade enhances the steady state splenic TFH program - PD-1 blockade selectively exaggerates a Type 2 like TFH module - GC TFR cells are minimally impacted by blockade - PD-1 restrains predicted TFH2 functional contacts with IgG1 GC B Cells

immunology↗

bioRxiv2021

Evolution of antigen-specific follicular helper T cell transcriptional programs across effector function and through to memory

Understanding how follicular helper T cells (TFH) regulate the specialization, maturation, and differentiation of adaptive B cell immunity is crucial for developing durable high-affinity immune protection. Using indexed-single cell molecular strategies, we reveal a skewed intra-clonal assortment of higher affinity TCR and the distinct molecular programming of the localized TFH compartment compared to emigrant conventional effector TH (ETH) cells. We find a temporal shift in BCR class switch which permits identification of inflammatory and anti-inflammatory modules of transcriptional programming that subspecialize TFH function before and during the germinal center (GC) reaction. Late collapse of this local primary GC reaction reveals a persistent post-GC TFH population which discloses a putative memory TFH program. These studies define specialized antigen-specific TFH transcriptional programs that progressively direct class-specific evolution of high-affinity B cell immunity and uncover the transcriptional program of a memory TFH population as the regulators of antigen recall. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/460841v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@17413c2org.highwire.dtl.DTLVardef@1bd505borg.highwire.dtl.DTLVardef@1e6bc99org.highwire.dtl.DTLVardef@167e6e9_HPS_FORMAT_FIGEXP M_FIG C_FIG SummaryDistinct inflammatory and anti-inflammatory antigen-specific TFH transcriptional programs regulate class-specific B cell maturation. Highlights- Skewed intra-clonal assortment of high affinity TCR into the TFH compartment - Significant temporal delay in anti-inflammatory IgG1 production - Inflammatory and anti-inflammatory transcriptional modules subspecialize TFH - Late GC collapse reveals a persisting post-GC putative memory TFH compartment

immunology↗

bioRxiv2021

Programming isotype specific plasma cell differentiation

Antibodies are produced across multiple isotypes with distinct properties that coordinate initial antigen clearance and confer long-term antigen-specific immune protection. Here, we interrogate the molecular programs of isotype-specific murine plasma cells (PC) following helper T cell dependent immunization and within established steady-state immunity. Using integrated single cell strategies, we reveal conserved and divergent components of the rapid effector phase of antigen-specific IgM+ versus inflammation modulating programs dictated by IgG2a/b+ PC differentiation. During antibody affinity maturation, the germinal center (GC) cycle imparts separable programs for post-GC inhibitory IgG1+ and inflammatory IgG2a/b+ PC to direct long-term cellular function. In the steady-state, two subsets of IgM+ and separate IgG2b+ PC programs clearly segregate from splenic IgA+ PC programs that emphasize mucosal barrier protection. These diverse isotype-specific molecular pathways of PC differentiation control complementary modules of antigen clearance and immune protection that could be selectively targeted for immunotherapeutic applications and vaccine design.

immunology↗