bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of Breast Reconstruction Using Inferiorly Based Dermal Flap for the Ptotic Breast
Authors: Calderon Thais , Skibba Kathryn EH , Hansen Trevor , Amalfi Ashley , Chen Elaina
Published: May 2022

Introduction

The use of an inferiorly based dermal flap (IBDF) with implant insertion allows for 1-step reconstruction of a ptotic breast after mastectomy. An IBDF allows for secondary protection of the inferior pole and provides a vascularized pocket for implant insertion. Previous literature has demonstrated the use of this surgical approach for optimal patient satisfaction and higher patient-reported outcomes.

For this approach, the dermal flap epidermis is removed before insetting; however, invaginations containing epithelial components may serve as a nidus for infection. There is no study that has compared the safety of an IBDF technique to standard reconstruction. We hypothesize that there is no increase in surgical complications in the IBDF approach versus standard reconstruction.

Methods

This is a single-institution retrospective chart review of all patients who underwent implant-based reconstruction from June 2016 through December 2020. Patients who did not have a permanent implant placed by December 2020 or had delayed reconstruction were excluded. Two cohorts were established: those who underwent immediate reconstruction after mastectomy via IBDF and reconstruction without an IBDF. Patient demographics, use of the IBDF technique, and surgical complications were recorded and compared.

Results

A total of 208 breasts were included: 52 breasts in the IBDF cohort and 156 breasts in the control cohort. There were no statistically significant differences between cohorts, except that the IBDF cohort has a significantly higher body mass index (mean = 30.9 vs 26.5, P ≤ .001).

There was no statistically significant difference in the rate of complications between the IBDF and control groups, including seroma (5.8% vs 3.8%), hematoma (3.8% vs 0.6%), wound dehiscence (0.0% vs. 1.9%), mastectomy flap necrosis (11.5% vs 6.4%), breast infection (5.8% vs 7.1%), implant salvage (0.0% vs 5.8%), and implant loss (5.8% vs. 5.8%), respectively.

Conclusions

Using an IBDF to reconstruct a ptotic breast immediately after mastectomy has a similar risk profile to an immediate standard breast reconstruction. This technique has resulted in optimal patient satisfaction scores and allows for a “one-stop reconstruction” of ptotic breasts that normally would undergo sequential revisions. In conclusion, immediate implant-based reconstruction of a ptotic breast after mastectomy using a IBDF can be performed safely.
Disparities in Access to Postmastectomy Breast Reconstruction: Does Living in a Specific ZIP Code Determine the Patient’s Reconstructive Journey?
Authors: Moroni Elizabeth A. , Bustos Samyd S. , Mehta Meeti , Munoz-Valencia Alejandro , Douglas Nerone K. O. , Bustos Valeria P. , Evans Steven , Diego Emilia J. , De La Cruz Carolyn
Published: May 2022

Background

Postmastectomy breast reconstruction (BR) has been shown to provide long-term quality of life and psychosocial benefits. Despite the policies initiated to improve access to BR, its delivery continues to be inequitable, suggesting that barriers to access have not been fully identified and/or addressed. The purpose of this study was to assess the influence of geographic location, socioeconomic status, and race in access to immediate BR (IBR).

Methods

An institutional review board–approved observational study was conducted. All patients who underwent breast cancer surgery from 2014 to 2019 were queried from our institutional Breast Cancer Registry. A geographical analysis was conducted using demographic characteristics and patient’s ZIP codes. Euclidean distance from patient home ZIP code to UPMC Magee Women's Hospital was calculated, and χ2, Student t test, Mann-Whitney, and Kruskal-Wallis tests was used to evaluate differences between groups, as appropriate. Statistical significance was set at P < 0.05.

Results

Overall, 5835 patients underwent breast cancer surgery. A total of 56.7% underwent lumpectomy or segmental mastectomy, and 43.3% underwent modified, total, or radical mastectomy. From the latter group, 33.5% patients pursued BR at the time of mastectomy: 28.6% autologous, 48.1% implant-based, 19.4% a combination of autologous and implant-based, and 3.9% unspecified reconstruction. Rates of IBR varied among races: White or European (34.1%), Black or African American (27.7%), and other races (17.8%), P = 0.022. However, no difference was found between type of BR among races (P = 0.38). Moreover, patients who underwent IBR were significantly younger than those who did not pursue reconstruction (P < 0.0001). Patients who underwent reconstruction resided in ZIP codes that had approximately US $2000 more annual income, a higher percentage of White population (8% vs 11% non-White) and lower percentage of Black or African American population (1.8% vs 2.9%) than the patients who did not undergo reconstruction.

Conclusions

While the use of postmastectomy BR has been steadily rising in the United States, racial and socioeconomic status disparities persist. Further efforts are needed to reduce this gap and expand the benefits of IBR to the entire population without distinction.
Considering light–matter interactions in the Friedmann equations
Authors: Vavryčuk V.
Published: May 2022

Recent observations indicate that the Universe is not transparent but partially opaque due to absorption of light by ambient cosmic dust. This implies that the Friedmann equations valid for the transparent universe must be modified for the opaque universe. This paper studies a scenario in which the opacity rises with redshift. In this case, the light–matter interactions become important, because cosmic opacity produces radiation pressure that counterbalances gravitational forces. The presented theoretical model assumes the Universe is expanding according to the standard FLRW metric but with the scale factor

a
(
t
)

depending on both types of forces: gravity as well as radiation pressure. The modified Friedmann equations predict a cyclic expansion/contraction evolution of the Universe within a limited range of scale factors with no initial singularity. The model avoids dark energy and removes some other tensions of the standard cosmological model. The paper demonstrates that considering light–matter interactions in cosmic dynamics is crucial and can lead to new cosmological models essentially different from the standard

Λ

CDM model. This emphasizes the necessity of new observations and studies of cosmic opacity and cosmic dust at high redshifts for more realistic modelling of the evolution of the Universe.
Epidemics on multilayer simplicial complexes
Authors: Fan Junfeng , Yin Qian , Xia Chengyi , Perc Matjaž
Published: May 2022

Simplicial complexes describe the simple fact that in social networks a link can connect more than two individuals. As we show here, this has far-reaching consequences for epidemic spreading, in particular in the context of a multilayer network model, where one layer is a virtual social network and the other one is a physical contact network. The social network layer is responsible for the transmission of information via pairwise or higher order 2-simplex interactions among individuals, while the physical layer is responsible for the epidemic spreading. We use the microscopic Markov chain approach to derive the probability transition equations and to determine epidemic outbreak thresholds. We further support these results with Monte Carlo simulations, which are in good agreement, thus confirming the analytical tractability of the proposed model. We find that information transmission rates are frequently low when actual disease transmission rates in the physical network are low or medium, and we show that this can be mitigated effectively by introducing 2-simplex interactions in the social network. The relative ease of introducing higher-order interactions in virtual social networks means that this could be exploited to inhibit epidemic outbreaks.
Dancing drives evolution of sexual size dimorphism in manakins
Authors: Shogren Elsie H. , Anciães Marina , Barske Julia , Cestari César , DuVal Emily H. , Gaiotti Milene G. , Johnson Erik I. , Kimball Rebecca T. , Marini Miguel A. , Ryder T. Brandt , Scholer Micah N. , Ungvári Judit , White Stewart A. , Boyle W. Alice
Published: May 2022

Body size mediates life history, physiology and inter- and intra-specific interactions. Within species, sexes frequently differ in size, reflecting divergent selective pressures and/or constraints. Both sexual selection and differences in environmentally mediated reproductive constraints can drive sexual size dimorphism, but empirically testing causes of dimorphism is challenging. Manakins (Pipridae), a family of Neotropical birds comprising approximately 50 species, exhibit a broad range of size dimorphism from male- to female-biased and are distributed across gradients of precipitation and elevation. Males perform courtship displays ranging from simple hops to complex aerobatic manoeuvres. We tested associations between sexual size dimorphism and (a) agility and (b) environment, analysing morphological, behavioural and environmental data for 22 manakin species in a phylogenetic framework. Sexual dimorphism in mass was most strongly related to agility, with males being lighter than females in species performing more aerial display behaviours. However, wing and tarsus length dimorphism were more strongly associated with environmental variables, suggesting that different sources of selection act on different aspects of body size. These results highlight the strength of sexual selection in shaping morphology—even atypical patterns of dimorphism—while demonstrating the importance of constraints and ecological consequences of body size evolution.
Neural activity patterns differ between learning contexts in a social fish
Authors: Rodriguez-Santiago Mariana , Jordan Alex , Hofmann Hans A.
Published: May 2022

Learning and decision-making are greatly influenced by context. When navigating a complex social world, individuals must quickly ascertain where to gain important resources and which group members are useful sources of such information. Such dynamic behavioural processes require neural mechanisms that are flexible across contexts. Here we examine how the social context influences the learning response during a cue discrimination task and the neural activity patterns that underlie acquisition of this novel information. Using the cichlid fish,
Astatotilapia burtoni
, we show that learning of the task is faster in social groups than in a non-social context. We quantify the neural activity patterns by examining the expression of Fos, an immediate-early gene, across brain regions known to play a role in social behaviour and learning (such as the putative teleost homologues of the mammalian hippocampus, basolateral amygdala and medial amygdala/BNST complex). We find that neural activity patterns differ between social and non-social contexts. Taken together, our results suggest that while the same brain regions may be involved in the learning of a cue association, the activity in each region reflects an individual's social context.
Scared to evolve? Non-consumptive effects drive rapid adaptive evolution in a natural prey population
Authors: Zhang Chao , Goitom Eyerusalem , Brans Kristien , De Meester Luc , Stoks Robby
Published: May 2022

Predators can strongly influence prey populations through both consumptive and non-consumptive effects. Nevertheless, most studies have focused on the consumptive effects in driving evolutionary changes. By integrating experimental evolution and resurrection ecology, we tested the roles of non-consumptive and consumptive effects in driving evolution in a
Daphnia magna
population that experienced strong changes in fish predation pressure. All resurrected genotypes were pooled, inoculated in outdoor mesocosms, and exposed to free-fish or caged-fish treatments. Non-consumptive effects induced rapid, repeatable changes in the clonal composition and associated genotypic trait changes that were similar in magnitude and direction to those imposed by killing. Both non-consumptive and consumptive effects caused a shift towards a dominance of the high-fish period clones that can perform better under fish predation, and this may be explained by the higher intrinsic growth rate of the high-fish period clones under predation risk. The genotypic trait changes (e.g. reduced body sizes, earlier maturation, more and smaller offspring) of the
Daphnia
in the mesocosm experiments were in the same direction as the adaptive trait shifts observed
in situ
through resurrection ecology. Our results demonstrate that non-consumptive effects can induce rapid adaptive evolution and may represent an overlooked driver of eco-evolutionary dynamics.
Heterosis counteracts hybrid breakdown to forestall speciation by parallel natural selection
Authors: Thompson Ken A. , Schluter Dolph
Published: May 2022

In contrast to ecological speciation, where reproductive isolation evolves as a consequence of divergent natural selection, speciation by parallel natural selection has been less thoroughly studied. To test whether parallel evolution drives speciation, we leveraged the repeated evolution of benthic and limnetic ecotypes of threespine stickleback fish and estimated fitness for pure crosses and within-ecotype hybrids in semi-natural ponds and in laboratory aquaria. In ponds, we detected hybrid breakdown in both ecotypes but this was counterbalanced by heterosis and the strength of post-zygotic isolation was nil. In aquaria, we detected heterosis in limnetic crosses and breakdown in benthic crosses, which is suggestive of process- and ecotype-specific environment-dependence. In ponds, heterosis and breakdown were three times greater in limnetic crosses than in benthic crosses, contrasting the prediction that the fitness consequences of hybridization should be greater in crosses among more derived ecotypes. Consistent with a primary role for stochastic processes, patterns differed among crosses between populations from different lakes. Yet, the observation of qualitatively similar patterns of heterosis and hybrid breakdown for both ecotypes when averaging the lake pairs indicates that the outcome of hybridization is repeatable in a general sense.
The ecology of wealth inequality in animal societies
Authors: Strauss Eli D. , Shizuka Daizaburo
Published: May 2022

Individuals vary in their access to resources, social connections and phenotypic traits, and a central goal of evolutionary biology is to understand how this variation arises and influences fitness. Parallel research on humans has focused on the causes and consequences of variation in material possessions, opportunity and health. Central to both fields of study is that unequal distribution of wealth is an important component of social structure that drives variation in relevant outcomes. Here, we advance a research framework and agenda for studying wealth inequality within an ecological and evolutionary context. This ecology of inequality approach presents the opportunity to reintegrate key evolutionary concepts as different dimensions of the link between wealth and fitness by (i) developing measures of wealth and inequality as taxonomically broad features of societies, (ii) considering how feedback loops link inequality to individual and societal outcomes, (iii) exploring the ecological and evolutionary underpinnings of what makes some societies more unequal than others, and (iv) studying the long-term dynamics of inequality as a central component of social evolution. We hope that this framework will facilitate a cohesive understanding of inequality as a widespread biological phenomenon and clarify the role of social systems as central to evolutionary biology.
Thermal regime during parental sexual maturation, but not during offspring rearing, modulates DNA methylation in brook charr (Salvelinus fontinalis)
Authors: Venney Clare J. , Wellband Kyle W. , Normandeau Eric , Houle Carolyne , Garant Dany , Audet Céline , Bernatchez Louis
Published: May 2022

Epigenetic inheritance can result in plastic responses to changing environments being faithfully transmitted to offspring. However, it remains unclear how epigenetic mechanisms such as DNA methylation can contribute to multigenerational acclimation and adaptation to environmental stressors. Brook charr (Salvelinus fontinalis), an economically important salmonid, is highly sensitive to thermal stress and is of conservation concern in the context of climate change. We studied the effects of temperature during parental sexual maturation and offspring rearing on whole-genome DNA methylation in brook charr juveniles (fry). Parents were split between warm and cold temperatures during sexual maturation, mated in controlled breeding designs, then offspring from each family were split between warm (8°C) and cold (5°C) rearing environments. Using whole-genome bisulfite sequencing, we found 188 differentially methylated regions (DMRs) due to parental maturation temperature after controlling for family structure. By contrast, offspring rearing temperature had a negligible effect on offspring methylation. Stable intergenerational inheritance of DNA methylation and minimal plasticity in progeny could result in the transmission of acclimatory epigenetic states to offspring, priming them for a warming environment. Our findings have implications pertaining to the role of intergenerational epigenetic inheritance in response to ongoing climate change.
Kitasatospora humi sp. nov., isolated from a tropical peat swamp forest soil, and proposal for the reclassification of Kitasatospora psammotica as a later heterotypic synonym of Kitasatospora aureofaciens
Authors: Klaysubun Chollachai , Srisuk Nantana , Duangmal Kannika
Published: May 2022

A polyphasic approach was used to describe strain RB6PN24T, a novel actinobacterium isolated from peat swamp forest soil collected from Rayong province, Thailand. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain belonged to the genus

Kitasatospora

and showed the highest sequence similarities to

Kitasatospora kifunensis

IFO 15206T (98.7 %) and

Kitasatospora acidiphila

MMS16-CNU292T (98.5 %). Strain RB6PN24T contained major amounts of meso-diaminopimelic acid, galactose, mannose and ribose in the whole-cell hydrolysates. MK-9(H6) and MK-9(H8) were the predominant menaquinones of the micro-organism. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, an unidentified lipid, four unidentified aminolipids and six unidentified phospholipids. Mycolic acids were not present. The major fatty acids were iso-C15 : 0, iso-C16 : 0, anteiso-C15 : 0, iso-C17:0, anteiso-C17 : 0 and C16 : 0. The draft genome size of strain RB6PN24T was 8.09 Mbp, with 72.1 mol% G+C content and predicted to contain at least 44 biosynthetic gene clusters encoding diverse secondary metabolites. Furthermore, the strain exhibited low average nucleotide identity and digital DNA–DNA hybridization values with

K. acidiphila

MMS16-CNU292T (89.1 %, 42.4 %) and

K. kifunensis

DSM 41654T (79.5 %, 25.5 %). The results of phenotypic, chemotaxonomic, genotypic and phylogenetic analyses revealed that strain RB6PN24T represents a novel species of the genus

Kitasatospora

, for which the name Kitasatospora humi sp. nov. is proposed. The type strain is RB6PN24T (=TBRC 14818T=NBRC 115116T). In addition, the comparison of the whole genome sequences and phenotypic features suggested that

Kitasatospora aureofaciens

and

Kitasatospora psammotica

belong to the same species. Therefore, it is proposed that

K. psammotica

is reclassified as a later heterotypic synonym of

K. aureofaciens

.
ICTV Virus Taxonomy Profile: Potyviridae 2022
Authors: Inoue-Nagata Alice K. , Jordan Ramon , Kreuze Jan , Li Fan , López-Moya Juan José , Mäkinen Kristiina , Ohshima Kazusato , Wylie Stephen J. ,   ICTV Report Consortium
Published: May 2022

The family Potyviridae includes plant viruses with single-stranded, positive-sense RNA genomes of 8–11 kb and flexuous filamentous particles 650–950 nm long and 11–20 nm wide. Genera in the family are distinguished by the host range, genomic features and phylogeny of the member viruses. Most genomes are monopartite, but those of members of the genus Bymovirus are bipartite. Some members cause serious disease epidemics in cultivated plants. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Potyviridae, which is available at ictv.global/report/potyviridae.
Identification of key molecules and biological processes in TCF21 treated tumor pericytes
Authors: Zhao Guofang , Zhang Donghong , Wang Mengshan
Published: May 2022

Colorectal cancer has become a major public health problem in the US. Transcription factor 21 (TCF21) is reported to be silenced in colorectal cancer tissues. However, the mechanism of TCF21 in tumor pericytes is still unclear. In our study, we aim to identify the key biological processes and signaling pathways by analyzing the RNA-seq data. The GSE200064 was produced by the Illumina NovaSeq 6000 (Homo sapiens). The KEGG and GO analyses showed that MAPK signaling pathway and complement/coagulation cascades are the major changed signaling pathways in the progression of tumor pericytes with overexpression of TCF21. Moreover, we identified several interactive molecules including VEGFA, MMP2, CCL2, COL3A1, COL1A2, CXCL12, ELN, PDGFRB, VWF, and APOE. These findings may benefit the study of colorectal cancer treatment.
Immunogenicity of BNT162b2 Vaccine Booster Dose in Patients with Inflammatory Bowel Disease Receiving Infliximab Combination Therapy: A Prospective Observational Study
Authors: Shehab Mohammad , Alrashed Fatema , Alfadhli Ahmad , Alsayegh Abdulwahab , Aldallal Usama , Cherian Preethi , Alkhair Irina , Thanaraj Thangavel Alphonse , Channanath Arshad , Dashti Ali A. , Albanaw Anwar , Ali Hamad , Abu-Farha Mohamed , Abubaker Jehad , Al-Mulla Fahd
Published: May 2022

Introduction

Few data exist regarding the immunogenicity of third dose of BNT162b2 relative to second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy.

Methods

This is prospective single center observational study conducted between January 1st, 2022 until February 28th, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine and have received two or three-dose of BNT162b2 vaccine. Patients were excluded if they were infected or had symptoms of SARS-CoV-2 previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40-45 weeks from the first dose of BNT162b2 in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated.

Results

162 patients with IBD and receiving infliximab combination therapy were recruited and the number of patients in each group was 81. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/mL (43, 192)] compared to patients who received the third booster dose [207 BAU/mL (181, 234)] (p = 0.003). Neutralizing antibody levels were also lower after the second dose [80 BAU/mL (21, 95)] compared to patients who received the third booster dose [96 BAU/mL (93, 99)] (p = <0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was higher (96.3%) than those in second dose group (90%)(p = 0.026). Percentage of patients who received third (booster) dose and achieved positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was lower (88.9%) in patients who received second dose only (p=0.009).

Conclusion

Most patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40-45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received 2 doses only compared to patients who received a third dose.
Structures of NF-κB p52 homodimer-DNA complexes rationalize binding mechanisms and transcription activation
Authors: Meshcheryakov Vladimir A. , Pan Wenfei , Li Tianjie , Wang Yi , Ghosh Gourisankar , Wang Vivien Ya-Fan
Published: May 2022

The mammalian NF-κB p52:p52 homodimer together with its cofactor Bcl3 activates transcription of κB sites with a central G/C base pair (bp), while it is inactive toward κB sites with a central A/T bp. To understand the molecular basis for this unique property of p52, we have determined its structure in complex with a P-selectin(PSel)-κB DNA (5’-GGGGTGACCCC-3’) (central bp is underlined) and variants changing the central bp to A/T or swapping the flanking bp. The structures reveal a nearly two-fold widened minor groove in the central region of the DNA as compared to all other currently available NF-κB-DNA complex structures, which have a central A/T bp. Molecular dynamics (MD) simulations show free DNAs exist in distinct preferred conformations, and p52:p52 homodimer induces the least amount of conformational changes on the more transcriptionally active natural PSel-κB DNA in the bound form. Our binding assays further demonstrate that the fast kinetics driven by entropy is correlated with higher transcriptional activity. Overall, our studies have revealed a novel conformation for κB DNA in complex with NF-κB and suggest the importance of binding kinetics, dictated by free DNA conformational and dynamic states, in controlling transcriptional activation for NF-κB.
Patterning of the female reproductive tract along antero-posterior and dorso-ventral axes is dependent on Amhr2+ mesenchyme in mice
Authors: Jia Shuai , Wilbourne Jillian , Crossen McKenna J , Zhao Fei
Published: May 2022

Morphogenesis of the female reproductive tract is regulated by the mesenchyme. However, the identity of the mesenchymal lineage that directs the patterning of the female reproductive tract has not been determined. Using in vivo genetic cell ablation, we identified Amhr2+ mesenchyme as an essential mesenchymal population in patterning the female reproductive tract. After partial ablation of Amhr2+ mesenchymal cells, the oviduct failed to develop its characteristic coiling due to decreased epithelial proliferation and tubule elongation during development. The uterus displayed a reduction in size and showed decreased cellular proliferation in both epithelial and mesenchymal compartments. More importantly, in the uterus, partial ablation of Amhr2+ mesenchyme caused abnormal lumen shape and altered the direction of its long axis from the dorsal-ventral axis to the left-right axis (i.e. perpendicular to the dorsal-ventral axis). Despite these morphological defects, epithelia underwent normal differentiation into secretory and ciliated cells in the oviduct and glandular epithelial cells in the uterus. These results demonstrated that Amhr2+ mesenchyme can direct female reproductive tract morphogenesis by regulating epithelial proliferation and lumen shape without affecting the differentiation of epithelial cell types.
A unique epigenomic landscape defines CD8+ tissue-resident memory T cells
Authors: Buquicchio Frank A. , Fonseca Raissa , Belk Julia A. , Evrard Maximilien , Obers Andreas , Qi Yanyan , Daniel Bence , Yost Kathryn E. , Satpathy Ansuman T. , Mackay Laura K.
Published: May 2022

Memory T cells provide rapid and long-term protection against infection and tumors. The memory CD8+ T cell repertoire contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. While these T cell populations have been well characterized in terms of differentiation potential and function, the epigenetic changes underlying memory T cell fate determination and tissue-residency remain largely unexplored. Here, we examined the single-cell chromatin landscape of CD8+ T cells over the course of acute viral infection. We reveal an early bifurcation of memory precursors displaying distinct chromatin accessibility and define epigenetic trajectories that lead to a circulating (TCIRC) or tissue-resident memory T (TRM) cell fate. While TRM cells displayed a conserved epigenetic signature across organs, we demonstrate that these cells exhibit tissue-specific signatures and identify transcription factors that regulate TRM cell populations in a site-specific manner. Moreover, we demonstrate that TRM cells and exhausted T (TEX) cells are distinct epigenetic lineages that are distinguishable early in their differentiation. Together, these findings show that TRM cell development is accompanied by dynamic alterations in chromatin accessibility that direct a unique transcriptional program resulting in a tissue-adapted and functionally distinct T cell state.

Graphical Abstract

Highlights

scATAC atlas reveals the epigenetic variance of memory CD8+ T cell subsets over the course of acute infection

Early bifurcation of memory precursors leads to circulating versus tissue-resident cell fates

Integrating transcriptional and epigenetic analyses identified organ-specific TRM cell regulators including HIC1 and BACH2

Epigenetic distinction of TRM cells and TEX cell subsets
Limiting distribution of X-chromosomal coalescence times under first-cousin consanguineous mating
Authors: Cotter Daniel J. , Severson Alissa L. , Carmi Shai , Rosenberg Noah A.
Published: May 2022

By providing additional opportunities for coalescence within families, the presence of consanguineous unions in a population reduces coalescence times relative to non-consanguineous populations. First-cousin consanguinity can take one of six forms differing in the configuration of sexes in the pedigree of the male and female cousins who join in a consanguineous union: patrilateral parallel, patrilateral cross, matrilateral parallel, matrilateral cross, bilateral parallel, and bilateral cross. Considering populations with each of the six types of first-cousin consanguinity individually and a population with a mixture of the four unilateral types, we examine coalescent models of consanguinity. We previously computed, for first-cousin consanguinity models, the mean coalescence time for X-chromosomal loci and the limiting distribution of coalescence times for autosomal loci. Here, we use the separation-of-time-scales approach to obtain the limiting distribution of coalescence times for X-chromosomal loci. This limiting distribution has an instantaneous coalescence probability that depends on the probability that a union is consanguineous; lineages that do not coalesce instantaneously coalesce according to an exponential distribution. We study the effects on the coalescence time distribution of the type of first-cousin consanguinity, showing that patrilateral-parallel and patrilateral-cross consanguinity have no effect on X-chromosomal coalescence time distributions and that matrilateral-parallel consanguinity decreases coalescence times to a greater extent than does matrilateral-cross consanguinity.
Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene
Authors: Makhlouf Melanie , D’Hulst Charlotte , Omura Masayo , Rosa Alessandro , Mina Raena , Bernal-Garcia Sergio , Lempert Eugene , Saraiva Luis R. , Feinstein Paul
Published: May 2022

In the mouse, more than 1,100 odorant receptors (ORs) are expressed in a monogenic and monoallelic fashion, referred to as singular gene expression. Using a 21bp singular-choice enhancer (x21), we radically increase representation of olfactory sensory neurons (OSNs) choosing a 5×21 enhanced OR transgene, but not overexpression of its mRNA on a per cell basis. RNA-sequencing and differential expression analysis identified 425 differentially expressed genes (DEGs). ORs make up 86% of all DEGs, of which 325 have decreased representation and 40 have increased representation. Underrepresented ORs include Class I, Class II and TAAR genes and within each of their respective olfactory bulb domains: DI, DII, and DIII (TAAR) we committedly observe multiple homogeneous glomeruli with an OR1A1-identity. The underrepresentation of endogenous, class-specific ORs across evolutionarily distinct cell types in favor of the expression of the 5×21-OR1A1 transgene argues that a common mechanism of singular gene choice is present for all OR-expressing OSNs.
Gaining insight into the allometric scaling of trees by utilizing 3d reconstructed tree models - a SimpleForest study
Authors: Hackenberg Jan , Disney Mathias , Bontemps Jean-Daniel
Published: May 2022

Forestry utilizes volume predictor functions utilizing as input the diameter at breast height. Some of those functions take the power formY=a∗Xb. In fact this function is fundamental for the biology field of allometric scaling theories founded round about a century ago. The theory describes the relationships between organs/body parts and the complete body of organisms.

With digital methods we can generate 3d forest point clouds non destructively in short time frames. SimpleForest is one free available tool which generates fully automated ground and tree models from high resoluted forest plots. Generated topological ordered cylinder models are called commonly QSMs.

We use SimpleForest QSMs an build a function which estimates the total supported wood volume at any given point of the tree. As input we use the supported soft wood volume for those query points. Instead of measuring directly the soft wood volume we use as a proxy the number of supported twigs. We argue with the pipe model theory for the correctness of the proxy.

We can use the named relationship to also filter our QSMs made of an open data set of tree clouds. The filter corrects overestimated radii. And we compare the corrected QSM volume against the harvested reference data for 66 felled trees. We also found QSM data of TreeQSM, a competitive and broadly accepted QSM modeling tool. Our RMSE was less than 40% of the tree QSM RMSE. And for other error measures, the r2adj. and the CCC, the relative improvement looked even better with 27% and 21% respectively.

We consider this manuscript as highly impactful because of the magnitude of quality improvement we do. The relation between soft volume and total volume distributions seems to be really strong and tree data can easily also be used as example data for the generic field of allometric scaling.
Interacting cortical gradients of neural timescales and functional connectivity and their relationship to perceptual behavior
Authors: Boring Matthew J. , Richardson R. Mark , Ghuman Avniel Singh
Published: May 2022

Cognitive acts take place over a large range of temporal scales. Numerous corresponding gradients in neurodynamic timescales and long-range cortical interactions are believed to provide organizational constraints to the brain and influence neural populations’ roles in cognition. However, it is unclear if gradients in various types of neural timescales and functional connectivity arise from related or distinct neurophysiological processes and if they influence behavior. Here, intracranial recordings from 4,090 electrode contacts in 35 individuals were used to systematically map gradients of multiple aspects of neurodynamics, neural timescales, and functional connectivity, and assess their interactions along category-selective ventral temporal cortex. Opposing functional connectivity gradients, with decreasing connectivity to visually responsive regions and increasing connectivity to regions that were not visually responsive, were observed along the ventral visual hierarchy. Endogenous neural timescales were correlated with functional connectivity to visually responsive regions after removing the effects of shared anatomical gradients, suggesting that these properties influence one another. Different stimulus evoked and endogenous timescales exhibited gradients with longer dynamics along the ventral visual hierarchy, but none of these timescales were significantly correlated with one another. This suggests that local neural timescales depend on neural and cognitive context and different timescales may arise through distinct neurophysiological processes. Furthermore, activity from neural populations with faster endogenous timescales and stronger functional connectivity to visually responsive regions was more predictive of perceptual behavior during a visual repeat detection task. These results reveal interrelationships and key distinctions among neural timescale and functional connectivity gradients that together can influence behavior.
The characteristics of high-dark-diversity habitats derived from lidar
Authors: Moeslund Jesper Erenskjold , Clausen Kevin Kuhlmann , Dalby Lars , Fløjgaard Camilla , Pärtel Meelis , Pfeifer Norbert , Hollaus Markus , Brunbjerg Ane Kirstine
Published: May 2022

A key aspect of nature conservation is knowledge of which aspects of nature to conserve or restore to favor the characteristic diversity of plants in a given area. Here, we used a large plant dataset with > 40.000 plots combined with airborne laser scanning (lidar) data to reveal the local characteristics of habitats having a high plant dark diversity – i.e., absence of suitable species – at national extent (> 43.000 km2). Such habitats have potential for reaching high realized diversity levels and hence are important in a conservation context. We calculated 10 different lidar based metrics (both terrain and vegetation structure) and combined these with 7 different field-based measures (soil chemistry and species indicators). We then used Integrated Nested Laplace Approximation for modelling plant dark diversity across 33 North European habitat types (open landscapes and forests) selected by the European communities to be important. In open habitat types high-dark-diversity habitats had relatively low pH, high nitrogen content, tall homogenous vegetation and overall relatively homogenous terrains (high terrain openness) although with a rather high degree of local microtopographical variations. High-dark-diversity habitats in forests had relatively tall vegetation, few natural-forest indicators, low potential solar radiation input and a low cover of small woody plants. Our results highlight important vegetation, terrain and soil related factors that managers and policymakers should be aware of in conservation and restoration projects to ensure a natural plant diversity, for example low nutrient loads, natural microtopography and open forests with old-growth elements such as dead wood and rot attacks.
Resetting of H3K4me2 during mammalian parental-to-zygote transition
Authors: Wang Chong , Shi Yong , Guo Jia , Hu Kaiyue , Wang Yaqian , Li Yang , Xu Jiawei
Published: May 2022

Upon sperm and oocyte fertilization, drastic histone modification reprograming occurs during preimplantation development. However, the global H3K4me2 landscape and its dynamics reprogramming in this period remains largely unknown. Herein we investigate the erasure and re-establishment of H3K4me2 in mouse GV, MII and embryos using an improved approach called Cleavage Under Targets and Release Using Nuclease (CUT&RUN) for histone modification with high-throughput sequencing. We find H3K4me2 extensively exists as a non-canonical pattern in mouse GV oocytes and early embryos. Interestingly, H3K4me2 is erased in MII oocyte and re-established in late 2-cell stage. Importantly, mouse embryos acquire widespread H3K4me2 in CpG-rich and hypomethylated regulatory regions in 4-cell stage, as well as 8-cell stage, but drastic changes happen upon ICM, these CpG-rich H3K4me2 regulatory regions then resolve to either active or repressed states. In summary, our study not only unveil that H3K4me2 transition from parental to zygote, but also provide a H3K4me2 profile during early embryo development, and this will enhance our comprehension to epigenetic reprogramming during mouse early development and in vitro fertilization.

Highlight

H3K4me2 present differential patterns in sperm and oocytes, as no-canonical pattern in GV oocytes but canonical of sperm in mouse.

GV H3K4me2 peaks were almost erased in MII oocytes, and reconstructed accompanying ZGA occurred, the first landscape of H3K4me2 during early mammalian development was provided.

Non-canonical H3K4me2 in mammalian embryos and pervasive H3K4me2 in CpG-rich regulatory regions in 4 and 8-cell embryos.

CpG-rich H3K4me2 regulatory regions resolve to either active or repressed states in ICM.
Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure
Authors: Walle Roman , Petitbon Anna , Fois Giulia R. , Varin Christophe , Montalban Enrica , Hardt Lola , Contini Andrea , Angelo Maria Florencia , Potier Mylène , Ortole Rodrigue , Oummadi Asma , De Smedt-Peyrusse Véronique , Adan Roger A , Giros Bruno , Chaouloff Francis , Ferreira Guillaume , de Kerchove d’Exaerde Alban , Ducrocq Fabien , Georges François , Trifilieff Pierre
Published: May 2022

Accumulating evidence points to dysregulations of common brain systems in eating disorders (ED), the Nucleus Accumbens (NAc) in particular. However, to which extent alterations in NAc activity contribute to ED-like dimensions remains unclear. Using chemogenetic manipulations of dopamine D1 receptor-expressing and D2-expressing neuronal subpopulations of the NAc in male mice, we assessed their respective roles in incentive processes, food intake and the balance between feeding and exercise-mediated energy expenditure. We found that D1-neurons facilitate effort for a food reward but decreased food intake, while D2-neurons have opposite effects. The anorexigenic influence of D1-neurons was accompanied by increased voluntary exercise while the orexigenic effect of D2-neurons was concomitant with decreased running, congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running. Chronic manipulations of each subpopulations had limited effects on energy balance. However, repeated activation of D1-neurons combined with inhibition of D2-neurons biased behavior toward activity-related energy expenditure leading to weight/fat loss, whilst the opposite manipulations favored energy intake and hence weight/fat gain. Strikingly, concomitant activation of D1-neurons and inhibition of D2-neurons precipitated weight loss in anorexia models. These results suggest that dysregulations of NAc dopaminoceptive neurons might be at the core of EDs.
Sigh breathing rhythm depends on intracellular calcium oscillations in a population of inspiratory rhythmogenic preBötzinger complex neurons in mice
Authors: Borrus Daniel S. , Grover Cameron J. , Smith Gregory D. Conradi , Del Negro Christopher A.
Published: May 2022

The preBötzinger Complex (preBötC) of the lower brainstem generates two breathing-related rhythms: one for inspiration on a timescale of seconds and another that produces larger amplitude sighs on the order of minutes. Their underlying mechanisms and cellular origins remain incompletely understood. We resolve these problems via a joint experiment and modeling approach. Blocking purinergic gliotransmission does not perturb either rhythm and imaging experiments show that both rhythms emanate from the same glutamatergic neuron population. We hypothesized that these two disparate rhythms emerge in tandem wherein recurrent excitation gives rise to inspiratory rhythm while a calcium oscillator generates sighs; there is no obligatory role for gliotransmission, hyperpolarization activated mixed cationic current (Ih) in neurons, or synaptic inhibition-mediated coupling of separate populations. We developed a mathematical model that instantiates our working hypothesis. Tests of model predictions validate the single-population rhythmogenic framework, reproducing disparate breathing-related frequencies and the ability for inspiratory and sigh rhythms to be separately regulated in support of respiration under a wide array of conditions. Here we show how a single neuron population exploits two cellular tool-kits: one involving voltage-dependent membrane properties and synaptic excitation for inspiratory breathing (eupnea) and an intracellular biochemical oscillator for sighs, which ventilate and maintain optimal function in the compliant mammalian lung.

SIGNIFICANCE STATEMENT

Breathing consists of two vital rhythms: one for eupnea that serves periodic physiological gas exchange and the other for sighs, which are larger breaths that occur minutes apart and serve to optimize pulmonary function. These rhythms with disparate frequencies emerge via a mechanism that is simpler than previously envisaged: it results from one neuron population (not two as previously thought) without need for gliotransmission or synaptic inhibition-mediated coupling of neuronal populations. We show that a low-frequency intracellular calcium oscillation underlies sighs and functions in parallel with the higher-frequency voltage-dependent network oscillation that drives eupnea. Exploiting two separate cellular tool kits enables quasi-independent breathing rhythms, which are unique features of breathing in mammals with compliant lungs.
NPC1 confers metabolic flexibility in Triple Negative Breast Cancer
Authors: O’Neill KI , Kuo LW , Williams MM , Lind HE , Crump LS , Hammond NG , Spoelstra NS , Caino MC , Richer JK
Published: May 2022

Triple negative breast cancer (TNBC) often undergoes at least partial epithelial-to-mesenchymal transition (EMT) to facilitate metastasis. Identifying EMT-associated characteristics can reveal novel dependencies that may serve as therapeutic vulnerabilities in this aggressive breast cancer subtype. We find that NPC1, which encodes the lysosomal cholesterol transporter Niemann-Pick Type C1 is highly expressed in TNBC as compared to estrogen receptor-positive (ER+) breast cancer and is significantly elevated in high grade disease. We demonstrate that NPC1 is directly targeted by microRNA-200c (miR-200c) a potent suppressor of EMT, providing a mechanism for its differential expression in breast cancer subtypes. Silencing of NPC1 in TNBC causes an accumulation of cholesterol-filled lysosomes and drives decreased growth on soft agar and invasive capacity. Conversely, overexpression of NPC1 in an ER+ cell line increases invasion and growth on soft agar. We further identify TNBC cell lines as cholesterol auxotrophs, however, they do not solely depend on NPC1 for adequate cholesterol supply. Genetic inhibition of NPC1 in TNBC cell lines led to altered mitochondrial function and morphology, suppression of mTOR signaling, and accumulation of autophagosomes. A small-molecule inhibitor of NPC1, U18666A, decreased TNBC proliferation and synergized with the chemotherapeutic drug, paclitaxel. This work suggests that NPC1 promotes aggressive characteristics in TNBC and identifies NPC1 as a potential therapeutic target.