bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular groundplan of male reproduction is partially preserved in parthenogenetic stick insects
Authors: Forni Giobbe , Mantovani Barbara , Mikheyev Alexander S. , Luchetti Andrea 
Published: November 2023

AbstractAfter the loss of a trait, theory predicts that the molecular machinery underlying its phenotypic expression should decay. Yet, empirical evidence is contrasting. Here, we test the hypotheses that (1) the molecular ground plan of a lost trait could persist due to pleiotropic effects on other traits and (2) that gene co-expression network architecture could constrain individual gene expression. Our testing ground has been theBacillusstick insect species complex, which contains close relatives that are either bisexual or parthenogenetic. After the identification of genes expressed in male reproductive tissues in a bisexual species, we investigated their gene co-expression network structure in two parthenogenetic species. We found that gene co-expression within the male gonads was preserved in parthenogens. Furthermore, parthenogens did not show relaxed selection on genes upregulated in male gonads in the bisexual species. As these genes were mostly expressed in female gonads, this preservation could be driven by pleiotropic interactions and an ongoing role in female reproduction. Connectivity within the network also played a key role, with highly connected - and more pleiotropic - genes within male gonad also having a gonad-biased expression in parthenogens. Our findings provide novel insight into the mechanisms which could underlie the production of rare males in parthenogenetic lineages; more generally, they provide an example of the cryptic persistence of a lost trait molecular ground plan, driven by gene pleiotropy on other traits and within their co-expression network.SignificanceLoss of traits commonly occurs in diverse lineages of organisms. Here we investigate what happens to genes and regulatory networks associated with these traits, using parthenogenetic insect species as a model. We investigated the fate of genes and gene regulatory networks associated with male gonads in a bisexual species in closely related parthenogens. Rather than showing signs of disuse and decay, they have been partially preserved in parthenogens. More highly pleiotropic genes in male gonads were more likely to have a gonad-biased expression profile in parthenogens. These results highlight the role of pleiotropy in the cryptic persistence of a trait molecular ground plan, despite its phenotypical absence.
Col4a2-eGFPmouse model reveals the molecular and functional dynamics of basement membrane remodelling in hair follicle morphogenesis
Authors: Wuergezhen Duligengaowa , Gindroz Eleonore , Morita Ritsuko , Hashimoto Kei , Abe Takaya , Kiyonari Hiroshi , Fujiwara Hironobu 
Published: November 2023

SummaryThe precisely controlled remodelling of the basement membrane (BM) is considered vital for morphogenesis. However, the molecular and tissue-level dynamics of the BM during morphogenesis and their functional significance remain largely unknown, especially in mammals, due to limited visualization tools. We developed knock-in mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we revealed a spatial gradient in the turnover rate of COL4A2 that is closely coupled with the BM expansion rate. The proliferation of epithelial progenitors coincided with the increased expansion of their underlying BM. Epithelial progenitors displaced with directionally expanding BM, but did not actively migrate on stable BM. The addition of a matrix metalloproteinase inhibitor delayed the turnover of COL4A2, restrained the expansion of the BM, and induced a directional shift in the division angle of epithelial progenitors, altering the hair follicle morphology. Our findings revealed spatially distinct BM dynamics within the continuous epithelial BM and affirmed their significance in orchestrating the proliferation, movement and fate of progenitor cells, as well as the macro-level shape of organs during development.
Multi-omics analyses of early-onset familial Alzheimer’s disease and Sanfilippo syndrome zebrafish models reveal commonalities in disease mechanisms
Authors: Barthelson Karissa , Protzman Rachael A , Snel Marten F , Hemsley Kim , Lardelli Michael 
Published: November 2023

AbstractSanfilippo syndrome (mucopolysaccharidosis type III, MPSIII) causes childhood dementia, while Alzheimer’s disease is the most common type of adult-onset dementia. There is no cure for either of these diseases, and therapeutic options are extremely limited. Increasing evidence suggests commonalities in the pathogenesis of these diseases. However, a direct molecular-level comparison of these diseases has never been performed. Here, we exploited the power of zebrafish reproduction (large families of siblings from single mating events raised together in consistent environments) to conduct sensitive, internally controlled, comparative transcriptome and proteome analyses of zebrafish models of early-onset familial Alzheimer’s disease (EOfAD,psen1Q96_K97del/+) and MPSIIIB (nagluA603fs/A603fs) within single families. We examined larval zebrafish (7 days post fertilisation), representing early disease stages. We also examined the brains of 6-month-old zebrafish, which are approximately equivalent to young adults in humans. We identified substantially more differentially expressed genes and pathways in MPS III zebrafish than in EOfAD-like zebrafish. This is consistent with MPS III being a rapidly progressing and earlier onset form of dementia. Similar changes in expression were detected between the two disease models in gene sets representing extracellular matrix receptor interactions in larvae, and the ribosome and lysosome pathways in 6-month-old adult brains. Cell type-specific changes were detected in MPSIIIB brains at 6 months of age, likely reflecting significant disturbances of oligodendrocyte, neural stem cell, and inflammatory cell functions and/or numbers. Our ‘omics analyses have illuminated similar disease pathways between EOfAD and MPS III indicating where efforts to find mutually effective therapeutic strategies can be targeted.
Protection conferred by intraperitoneal Group AStreptococcusimmunization relies on macrophages and IFN-γ but not on concurrent adaptive immune responses
Authors: Emami Shiva , Westerlund Elsa , Converso Thiago Rojas , Johansson-Lindbom Bengt , Persson Jenny J 
Published: November 2023

AbstractGroup AStreptococcus(GAS;Streptococcus pyogenes) is an important bacterial pathogen estimated to cause over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae in the world yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into >200 distinctemm(M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyze the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and although significant levels of GAS-specific antibodies are produced, these are redundant for protection. Instead, our data show that the immunization-dependent protection in this model is induced in the absence of B and T cells, is accompanied by an altered cytokine profile upon subsequent infection and requires macrophages and the macrophage-activating cytokine IFN-γ. To our knowledge these findings are the first to suggest that GAS has the ability to induce forms of trained innate immunity. Taken together, the current study reveals a novel mechanism of the innate immune system in response to GAS infections that potentially could be leveraged for future development of effective vaccines.Author summaryThe bacterium Group A Streptococcus (GAS) causes many hundred million infections and around 500.000 deaths in the world every year. GAS can give rise to a wide spectrum of diseases ranging from mild strep throat to life-threatening necrotizing fasciitis (often referred to as “flesh-eating disease”). There is currently no vaccine available for this pathogen, much due to our incomplete knowledge of how the immune system reacts to different GAS infections, what immune responses are in fact required for long-term protection and how these are generated. Here we show that protective immunity arising after immunization through the intraperitoneal (ip) cavity requires multiple injections using heat killed GAS. Surprisingly, although typical adaptive immune responses are activated and generate production of GAS-specific antibodies these are redundant for protection, which instead hinges on macrophages and the cytokine IFN-γ. Our findings suggest that ip GAS immunizations trigger what is known as ‘trained immunity’, where innate immune cells become imprinted to respond with increased efficiency towards subsequent infection. Overall, these observations highlight a previously unknown ability of GAS to induce non-canonical forms of protective immunity, discoveries that may significantly contribute to our thinking about how the immune system reacts to such infections and broaden the scope for future vaccine strategies.
S RNA Intergenic Deletions Drive Viral Interference during Arenavirus Infections
Authors: Hackbart Matthew , López Carolina B. 
Published: November 2023

ABSTRACTArenaviruses, a family of negative-sense RNA viruses spread by rodents, are a leading cause of severe hemorrhagic fever in humans. Due to a paucity of antivirals and vaccines for arenaviruses, there is a need to identify new mechanisms for interfering with arenavirus replication. In several negative-sense RNA viruses, natural viral interference results from the production of non-standard viral genomes (nsVGs) that activate the innate immune system and/or compete for essential viral products. Although it is well established that arenaviruses produce strong interfering activities, it is unknown if they produce interfering nsVGs. Here we show that arenaviruses produce deletions within the intergenic region of their Small (S) RNA genome, which prevents the production of viral mRNA and protein. These deletions are more abundant when arenaviruses are grown in high-interfering conditions and are associated with inhibited viral replication. Overall, we found that arenaviruses produce internal deletions within the S RNA intergenic region that are produced by arenaviruses and can block viral replication. These natural arenavirus interfering molecules provide a new target for the generation of antivirals as well as an alternative strategy for producing attenuated arenaviruses for vaccines.AUTHOR SUMMARYArenaviruses are hemorrhagic fever-causing pathogens that infect millions of people a year. There are currently no approved antivirals that target arenaviruses and understanding natural mechanisms that inhibit arenavirus replication is crucial for the development of effective therapeutics. Here, we identify multiple deletions within arenavirus genomes that are associated with the inhibition of viral replication. We show that these deletions prevent viral protein production through the removal of the intergenic region of the viral genome. These deletions were found in all arenaviruses tested in this study representing a novel mechanism for development of new antivirals and vaccines that broadly target the arenavirus family.
Opportunity nest egg: insights on the nutritional ecology, life history and captive management of three species of kiwi (Apteryxspp.) chick from Operation Nest Egg zoo hand-rearing records
Authors: Gray L.J. , Mitchell B.A. , Milner-Bradford I.L. , Keller L. , Bell G. , McGuire K.J. , Travers C. 
Published: November 2023

ABSTRACTZoo data collected by keepers while looking after endangered species are increasingly recognised as important scientific resources. As chicks, New Zealand’s threatened kiwi (Apteryxspp.) are subject to the protective conservation programme Operation Nest Egg (ONE), during which growth, developmental and life history data are recorded. We have conducted comparative analyses on hand rearing records from 306 chicks, from Coromandel, Eastern and Western populations of Brown kiwi (A. mantelli), and rowi (A. rowi) and Haast tokoeka (A. australis“Haast”). We analysed chick responses to an old dietvs. a new kiwi diet, introduced in 2017. Both diets are fixed nutrient ratio mixtures. The old diet was high-protein, low-energy, while the new diet is high-fat, high-energy, with better micronutrient levels. We found Coromandel chicks, who originate from the environmentally variable Kūaotunu Peninsula, grow the most efficiently overall on either diet, indicating they may be nutritional generalists. Western and Eastern chicks’ growth efficiency was intermediate, while the South Island species grew the least efficiently on either diet.Rowi chicks developed the fastest overall on either diet, while Haast tokoeka chicks developed the most slowly, especially on the new diet. Rowi chicks therefore had to eat large volumes of either diet over a short time to maintain their rapid development, while Haast chicks were required to eat large volumes, especially of the new diet, over a protracted developmental period. This situation may have led South Island chicks to over-consume one or another diet component, with likely health consequences. Neither diet was obviously superior for chick wellbeing overall, though the new diet better supported chicks that needed hand feeding. This work demonstrates different genetic populations of kiwi differ in their physiological responses to nutrition. As ONE is ongoing, tailored diets for chicks from each genetic group should be developed, and we present methods to achieve this. In our life history trait analyses, we found chick starting size (hatch mass) did not significantly influence growth efficiency across kiwi genetic group, nor did chick sex. We identified that chicks malpositioned as embryos were more likely to require extended periods of hand feeding, and that Eastern males produce more malpositioned embryos than other populations. Our study shows that effective zoo records can be used to improve captive care, to stimulate future research to refine species management practices, and to explore fundamental questions of life history evolution in wild and captive populations.
Riparian forests shape trophic interactions in detrital stream food webs
Authors: Oester Rebecca , Altermatt Florian , Bruder Andreas 
Published: November 2023

AbstractFreshwater and terrestrial biodiversity is linked through resource flows. For example, subsidies from the riparian vegetation form the base of food webs in small streams. Despite the key role of detritivores in these food webs, consequences of altered resource availability and riparian vegetation type on their trophic strategies are largely unknown. Therefore, we experimentally tested direct and indirect effects of riparian vegetation type on trophic interactions and dietary imbalances of detritivores. We used stoichiometric and isotopic differences between consumers and resources as functional measures of trophic link strength. Our results show that the lack – compared to the presence – of riparian forests directly affected both stoichiometric and isotopic differences in detrital food webs, yet with diverging patterns between resources and consumers, ultimately leading to aquatic-terrestrial decoupling. Consequently, our findings demonstrate that riparian forests are essential for aquatic food webs by influencing both organisms and interactions networks.
Utilization of a Clark electrode device as a respirometer for small insects: a convincing test on ants allowing to detect discontinuous respiration
Authors: Kervella Maïly , Cansell Céline , Criscuolo François , Bouillaud Frederic 
Published: November 2023

AbstractRespirometry provides a direct measure of an organism’s respiration, which is a significant component of its metabolic rate. Amongst ants, variations in lifespan between different social castes (such as workers and queens) can be substantial, varying according to the species. As metabolic rate is higher in short-living species, we aimed to establish how metabolic rate and longevity may have coevolved within ant’s casts. As a first methodological step, we validate here the use of a Clark electrode initially design for measuring mitochondrial respiration control pathways, for flow-through oxygen consumption in ant, by comparison with stop flow oxygen consumption and carbon dioxide production utilizing the indirect calorimetry methodology. The global aim is to provide a reliable methodology to conduct accurate comparisons of metabolic rates within and among ant species. As expected, using Clarck electrode entails high time resolution and revealed that queens and workers exhibited discontinuous respiration, with episodes of apnea up to 20 minutes.
Phosphatidic Acid Dependent Recruitment of Microtubule Motors to Spherical Supported Lipid Bilayers forIn-vitroMotility Assays
Authors: Kumar Pankaj , Sanghavi Paulomi , Chaudhury Dwiteeya , Mallik Roop 
Published: November 2023

ABSTRACTA variety of membrane-bound vesicles are transported by the kinesin and dynein motor proteins respectively towards plus and minus ends of microtubules inside cells. How specific lipids, particularly rare lipids, bind and activate motors on the vesicle membrane and the biological consequences thereof are poorly understood. Here we preparesphericalsupported lipid bilayers (SLBs) consisting of a latex bead enclosed within a membrane that contains phosphatidic acid (PA). When incubated with motor-protein enriched fractions fromDictyosteliumor from Rat brain, PA-coated SLBs exhibit robust motion alongin-vitropolymerized microtubules. We quantify the activity of SLB-bound motors by measuring their force generation against an Optical trap on polarity-labelled microtubules. Such experiments reveal that PA recruits dynein-dynactin fromDictyostelium, but kinesin-1 from rat brain fractions to drive SLB motion. Kinesin-1 is able to dominate over dynein when dynactin, an activator of dynein, is deficient on SLBs. We demonstrate how inhibiting only kinesin can block both kinesin and dynein activity on a cargo, thus providing an explanation for the long-standing “paradox of co-dependence” in the field of intracellular transport. We also find that as the size of a motor-driven SLB increases, the SLB is able to reverse direction more easily along a microtubule. This observation provides clues as to how micron-sized cargoes are efficiently able to navigate the crowded cytoskeletal space inside cells.
Origin, age, and metabolisms of dominant anammox bacteria in the global oxygen deficient zones
Authors: Zhao Rui , Zhang Irene H. , Jayakumar Amal , Ward Bess B. , Babbin Andrew R. 
Published: November 2023

AbstractAnammox bacteria inhabiting oxygen deficient zones (ODZs) are a major functional group mediating fixed nitrogen loss and thus exerting a critical control on the nitrogen budget in the global ocean. However, the diversity, origin, and broad metabolisms of ODZ anammox bacteria remain unknown. Here we report two novel metagenome-assembled genomes ofScalindua, which represent most, if not all, of the anammox bacteria in the global ODZs. Beyond the core anammox metabolism, both organisms contain cyanase and the more dominant one encodes a urease, indicating ODZ anammox bacteria can utilize cyanate and urea in addition to ammonium. The first ODZScalindualikely derived from the benthos ∼200 million years ago. Compared to benthic strains of the same clade, ODZScalinduauniquely encode genes for urea utilization but lost genes related to growth arrest, flagellum synthesis, and chemotaxis, presumably for adaptation to the anoxic water column.
SARS-CoV-2 infection leads to sustained testicular injury and functional impairments in K18 hACE2 mice
Authors: Giannakopoulos Stefanos , Ward Monika A , Bakse Jackson , Pak Jin , Nerurkar Vivek R , Tallquist Michelle D , Verma Saguna 
Published: November 2023

AbstractCompromised male reproductive health is one of the symptoms of long COVID with a decrease in male fertility markers including testosterone levels and sperm count for months in recovering patients. However, the long-term impact of SARS-CoV-2 infection on testicular injury and underlying mechanisms remains unknown. We previously demonstrated a disrupted tissue architecture with no evidence of virus replication in the testis during the acute stage of the disease in K18-hACE2 mice. Here, we systematically delineate the consequences of SARS-CoV-2 infection on the testis injury and function both during the acute stage of the disease and up to 4 weeks after infection in survivor K18-hACE2 mice. The gross morphological defects included sloughing of healthy spermatids and spermatocytes into the lumen, lack of lumen, and increase in apoptotic cells that sustained for at least 2 weeks after infection. Testis injury correlated with systemic and testicular inflammation, and infiltration of immune cells in the interstitial space and seminiferous tubules. Transcriptomic analysis identified dysregulation of key pathways of testicular immune homeostasis, spermatogenesis, and cell death at the symptomatic and short-term recovery stages. Further, a significant reduction in testosterone levels was associated with transient reduction in sperm count and mouse fertility. Most of the testicular impairments except testosterone levels were resolved within 4 weeks, which is almost one spermatogenesis cycle in mice. These findings provide much-needed mechanistic insights beyond our current understanding of testicular pathogenesis, suggesting that recovering COVID-19 patients should be closely monitored to rescue the pathophysiological effects on male reproductive health.