bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans
Authors: Gang Spencer S. , Grover Manish , Reddy Kirthi C. , Raman Deevya , Chang Ya-Ting , Ekiert Damian C. , Barkoulas Michalis , Troemel Emily R. 
Published: July 2022

AbstractRegulation of immunity throughout an organism is critical for host defense. Previous studies in the nematode Caenorhabditis elegans have described an “ON/OFF” immune switch comprised of the antagonistic paralogs PALS-25 and PALS-22, which regulate resistance against intestinal and epidermal pathogens. Here, we identify and characterize a PALS-25 gain-of-function mutant protein with a premature stop (Q293*), which we find is freed from physical repression by its negative regulator, the PALS-22 protein. PALS-25(Q293*) activates two related gene expression programs, the Oomycete Recognition Response (ORR) against natural pathogens of the epidermis, and the Intracellular Pathogen Response (IPR) against natural intracellular pathogens of the intestine. A subset of ORR/IPR genes is upregulated in pals-25(Q293*) mutants, and they are resistant to oomycete infection in the epidermis, and microsporidia and virus infection in the intestine, but without compromising growth. Surprisingly, we find that activation of PALS-25 seems to primarily stimulate the downstream bZIP transcription factor ZIP-1 in the epidermis, which leads to upregulation of gene expression in both the epidermis and in the intestine. Interestingly, we find that this epidermal-to-intestinal signaling promotes resistance to the N. parisii intestinal pathogen, demonstrating cross-tissue protective immune induction from one epithelial tissue to another in C. elegans.Author summaryMulticellular organisms need to monitor the health and function of multiple tissues simultaneously to respond appropriately to pathogen infection. Here, we study an ON/OFF switch in the roundworm C. elegans that controls immune responses to diverse natural pathogens of the skin and gut. We show a physical association between the ‘ON switch’ protein PALS-25 and the ‘OFF switch’ protein PALS-22, and that this association is disrupted in a mutant, activated form of PALS-25. When either PALS-22 is lost, or PALS-25 is activated, a downstream immune regulator ZIP-1 is activated specifically in the skin but not the gut. Excitingly, our findings show that skin-specific loss of PALS-22 or skin-specific activation of PALS-25 can induce immune responses in the worm gut. These findings highlight the coordination of immune responses across different tissues that are commonly infected by microbial pathogens.
Recognition of non-self is necessary to activate Drosophila’s immune response against an insect parasite
Authors: Leitão Alexandre B. , Arunkumar Ramesh , Day Jonathan P. , Hanna Nancy , Devi Aarathi , Hayes Matthew P. , Jiggins Francis 
Published: July 2022

AbstractInnate immune responses can be activated by pathogen-associated molecular patterns (PAMPs) or danger signals released by damaged tissues. As PAMPs are typically conserved across broad groups of pathogens but absent from the host, it is unclear whether they allow hosts to recognize parasites that are phylogenetically related to themselves, such as parasitoid wasps infecting insects. Parasitoids must penetrate the cuticle of Drosophila larvae to inject their eggs. In line with previous results, we find that the danger signal of wounding triggers the differentiation of specialized immune cells called lamellocytes. However, using oil droplets to mimic infection by a parasitoid wasp egg, we find that the activation of melanization response that kills parasitoids also requires exposure to a parasitoid wasp molecule that acts as a PAMP. The unidentified factor enhances the transcriptional response in hemocytes and induces a specific response in the fat body that includes Tep1, which is essential for efficient melanization. We conclude that a combination of danger signals and PAMPs are required activate Drosophila’s immune response against parasitic insects.
Evolutionary survival strategies of the female giant panda: optimizing energy resources and expenditure prior to pregnancy by postponing corpus luteum reactivation
Authors: Wauters Jella , Wilson Kirsten S. , Bouts Tim , Vancsok Catherine , Mulot Baptiste , Leclerc Antoine , Haapakoski Marko , Kok José , Kühne Ragnar , Ochs Andreas , McNeilly Alan S. , Rae Mick , Andrew Ruth , Duncan W. Colin , Girling Simon J. , Zhou Quang , Li Rengui , Zhou Yingmin , Cai Kailai , Liu Yuliang , Hou Rong , Valentine Iain , Hildebrandt Thomas B. , Li Desheng , Vanhaecke Lynn 
Published: July 2022

AbstractThe giant panda reproductive physiology shows important similarities with at least six of the eight existing bear species: the occurrence of diapause and/or pseudopregnancy is commonly described in bears. Nevertheless, significant differences including the earlier breeding season with - in general - a single estrus, a shorter delay of implantation and a more variable birth season, indicate an evolutionary adaptation from the seasonal reproductive traits described in hibernating bear species.In this study we aimed to determine true pregnancy length for giant pandas and to open the discussion on the peculiarities of giant panda reproductive biology, more specifically focusing on the rationale behind their short-seasoned reproductive cycle compared to the other bear species.For this purpose, metabolic (body weight and fecal output) profiles were matched with endocrine changes, mainly urinary progesterone metabolites, in 5 pregnant, 8 non-birth and 6 pseudopregnant cycles of 6 female giant pandas.Pregnancy in giant pandas lasts only 42 days from early reactivation of the corpora lutea (CLs) until birth. In addition, our findings urged the need to redefine the generally accepted biphasic progesterone profile into a triphasic primary progesterone rise (corpus luteum dormancy (CLD) I, II and III) prior to entering the active luteal phase (= secondary progesterone rise). Two episodes of progesterone increase (CLDII: 81.20 ± 5.85 days versus CLDIII: 60.80 ± 3.83 days prior to birth for pregnant cycles) were identified, respectively corresponding to CL reactivation (74-88 days prior to birth) and implantation (± 60 days prior to birth) in other bear species. The progesterone concentration during CLDIII was higher in pregnant cycles, indicating a potential communication between maternal tissues and blastocyst(s) enhancing progesterone concentrations and thus allowing optimal priming of uterine tissues to better prepare for blastocyst reactivation/development. Compared with other bear species, giant pandas seem to shorten the active luteal phase, and thus pregnancy, by approximately 30 days by actively postponing CL reactivation.Potential mechanisms in play overruling and suppressing the evolutionary conserved photoperiodical triggers of CL reactivation are discussed while a parallel study will further elaborate on the CL dynamics during giant panda gestation.
Critical analysis of radical scavenging properties of atorvastatin in methanol recently estimated via density functional theory
Authors: Bâldea Ioan 
Published: July 2022

AbstractIn this communication we draw attention on serious flaws that plague recently reported antioxidant properties of atorvastatin (ATV) in methanol. First and foremost, we emphasize that the O-H bond dissociation energies (BDE) of about 400kcal/mol previously reported are completely wrong. Further, we present results refuting the previous claim that the proton affinity (PA) of ATV is smaller than that of the ascorbic acid. That unfounded claim relies on incorrect data for PA’s ascorbic acid (which we correct here) circulated in the literature. Further, we correct the values of the chemical reactivity indices (e.g., chemical hardness, electrophilicity index, electroaccepting and electrodonating powers), which were inadequately estimated previously via Kohn-Sham HOMO and LUMO energies. Finally, our updated values for O–H bond dissociation enthalpy (BDE = 91.4 kcal/mol) and electron transfer enthalpy (ETE = 105.7kcal/mol) tentatively suggest that direct H-atom transfer (HAT) and sequential proton loss electron transfer (SPLET) may coexist.
VSTM1-v2 does not drive human Th17 cell differentiation
Authors: von Richthofen Helen J. , Hafkamp Florianne M.J. , van Haperen Anouk , de Jong Esther C. , Meyaard Linde 
Published: July 2022

AbstractSignal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of neutrophils, which is inhibited by SIRL-1 ligation. VSTM1-v2 is a soluble isoform of SIRL-1, which was previously proposed to function as a Th17 polarizing cytokine. Here, we investigated the effect of VSTM1-v2 on DC-driven Th17 cell development. Neutrophils induced DC-driven Th17 cell differentiation, which was not enhanced by VSTM1-v2. Similarly, we found no effect of VSTM1-v2 on cytokine-driven Th17 cell development. Thus, our results do not support a role for VSTM1-v2 in Th17 cell differentiation.
Methyl-SNP-seq reveals dual readouts of methylome and variome at molecule resolution
Authors: Yan Bo , Wang Duan , Vaisvila Romualdas , Sun Zhiyi , Ettwiller Laurence 
Published: July 2022

AbstractCovalent modifications of genomic DNA are crucial for most organisms to survive. Amplicon-based high throughput sequencing technologies erase all DNA modifications to retain only sequence information for the four canonical nucleobases, necessitating specialized technologies for ascertaining epigenetic information. To also capture base modification information, we developed Methyl-SNP-seq, a technology that takes advantage of the complementarity of the double helix to extract the methylation and original sequence information from a single DNA molecule. More specifically, Methyl-SNP-seq uses bisulfite conversion of one of the strands to identify cytosine methylation while retaining the sequence of the other strand. As both strands are locked together to link the dual readouts on a single paired-end read, Methyl-SNP-seq allows detecting methylation status of any DNA even without a reference genome. Because one of the strands retains the original 4 nucleotide composition, Methyl-SNP-seq can also be used in conjunction with standard sequence-specific probes for targeted enrichment and amplification. We demonstrate the usefulness of this technology in a broad spectrum of applications ranging from allele-specific methylation analysis in humans to identification of methyltransferase specificity in complex bacterial communities.
The robustness of phylogenetic diversity indices to extinctions
Authors: Manson Kerry 
Published: July 2022

AbstractPhylogenetic diversity indices provide a formal way to apportion evolutionary history amongst living species. Understanding the properties of these measures is key to determining their applicability in conservation biology settings. In this work, we investigate some questions posed in a recent paper by Fischer, Francis & Wicke appearing inSystematic Biology(Vol. 72(3), 2023). In that paper, it is shown that under certain extinction scenarios, the ranking of the surviving species by their Fair Proportion index scores may be the complete reverse of their ranking beforehand. Our main results here show that this behaviour extends to a large class of phylogenetic diversity indices, including the Equal-Splits index. We also provide a necessary condition for reversals of Fair Proportion rankings to occur on phylogenetic trees whose edge lengths obey the ultrametric constraint. Specific examples of rooted phylogenetic trees displaying these behaviours are given and the impact of our results on the use of phylogenetic diversity indices more generally is discussed.
Host-enemy interactions provide limited biotic resistance for a range-expanding species via reduced apparent competition
Authors: Prior Kirsten M. , Jones Dylan G. , Meadley-Dunphy Shannon A. , Lee Susan , Milks Alyson K. , Daughton Sage , Forbes Andrew A. , Powell Thomas H. Q. 
Published: July 2022

AbstractAs species ranges shift in response to anthropogenic change, they lose coevolved or coadapted interactions and gain novel ones in recipient communities. Range-expanding species may lose or experience weak antagonistic interactions with competitors and enemies, and traits of interacting species will determine the strength of interactions. We leveraged a poleward range expansion of an oak gall wasp that co-occurs on its host plant with other gall wasp species and interacts with shared natural enemies (largely parasitoid wasps). We created quantitative host-parasitoid interaction networks by sampling galls on 400 trees. We compared network structure and function and traits of hosts and parasitoids in the native and expanded range. Interaction networks were less diverse in the expanded range, with low complementarity of parasitoid assemblages among hosts. While whole networks were more generalized in the expanded range, interactions with the range-expanding species were more specialized. This was not due to a loss of specialist enemies but weak apparent competition by shared generalist enemies. Phenological divergence of enemy assemblages attacking the novel and co-occurring hosts was greater in the expanded range that may contribute to weak apparent competition. Given the rate and extent of anthropogenic-driven range expansions, it is pressing to uncover how complex biotic interactions are reassembled.
Nutrition-sensitive Agriculture – Is it possible in Morogoro Rural District? Awareness and practices among farmers
Authors: Sanga Innocent , Msuya John 
Published: July 2022

AbstractAccording to FAO (2017), nutrition-sensitive agriculture is an approach that seeks to ensure the production of a variety of affordable, nutritious, culturally appropriate and safe foods in adequate quantity and quality to meet the dietary requirements of populations in a sustainable manner. This study focused on analyzing ways in which the concept is implemented and assessing its awareness among the key nutrition stakeholders. These included government officials from village, ward and district levels, NGOs, agriculture inputs suppliers, food vendors and grain millers. Cross - sectional study design was employed and information from respondents were collected by using semi-structured questionnaires, key informant interviews and transect walk. Data analysis was conducted by using SPSS version 20. It was found that home gardening (85.3%) and livestock keeping (57.4%) were the most practiced ways of nutrition-sensitive agriculture. Other ways, including use of biofortified crops, fish farming, use of watering techniques in production of fruits and vegetables, use of soil fertility conserving techniques and using improved food crop varieties were hardly practiced. Above 90% of household heads knew the importance of agriculture to nutrition being a source of food for household consumption, a source of income and employment, makes easy to access nutrient dense foods in the household and ensuring food security. The study also observed high awareness about the concept even though, the actual implementation was low. It was concluded that, low economic status among the rural poor farmers is the major reasons that have led to the observed low practices of other studied ways of agriculture that are nutrition sensitive. It is recommended that, all key stakeholders should work together to subsidize seeds and other agro-inputs which are needed by the farmers to practice these ways.
Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars
Authors: Martínez-Zamudio Ricardo Iván , Stefa Alketa , Nabuco José Américo , Vasilopoulos Themistoklis , Simpson Mark , Doré Gregory , Roux Pierre-François , Galan Mark A. , Chokshi Ravi J. , Bischof Oliver , Herbig Utz 
Published: July 2022

SummaryAlthough oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells can escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors for escape from OIS and identify ‘senescence-associated chromatin scars (SACS)’ as an epigenetic memory of OIS, detectable during colorectal cancer progression. POU2F2 levels are elevated already in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape to promote senescence escape and reveal POU2F2 gene signatures and SACS as valuable biomarkers with diagnostic and prognostic potential.
Biofunctional matrix models reveal mineral-dependent mechanoregulation of bone metastatic breast cancer
Authors: Choi Siyoung , Whitman Matthew A. , Shimpi Adrian A. , Sempertegui Nicole D. , Chiou Aaron , Druso Joseph E. , Verma Akanksha , Lux Stephanie C. , Cheng Zhu , Paszek Matthew , Elemento Olivier , Estroff Lara A. , Fischbach Claudia 
Published: July 2022

AbstractBone metastasis is a leading cause of breast cancer-related deaths and often initiated by tumor cell dissemination to osteogenic niches. During new bone formation, osteoblasts first deposit osteoid, the collagen I-rich, unmineralized component of bone ECM, within which carbonated hydroxyapatite nanoparticles subsequently form. However, it remains elusive how bone matrix mineralization dictates tumor cell phenotype due in part to the lack of relevant model systems. Using biofunctional, collagen I-based bone matrix models with physiological, intrafibrillar mineralization, we show that mineralization inhibits proliferation, while inducing a stem-like phenotype in tumor cells. These changes were due to reduced mechanosignaling contradicting the conventional assumption that increased rigidity caused by mineralization stimulates metastatic progression. Our findings are translationally relevant as the presence of mineral reduced tumor growthin vivoand upregulated a gene signature that correlated with decreased patient mortality. Our results could help explain why decreased bone mineral density increases the risk for bone metastasis in patients and highlight that bone metastasis models should integrate organic and inorganic matrix components in a manner that mimics physiological mineralization.
Molecular basis for the pheromone-mediated feeding preference of early-instar Mythimna separata larvae
Authors: Liu Jiyuan , Cheng Shichang , Zhou Tong , Li Ruichi , Tian Zhen 
Published: July 2022

AbstractInsect sex pheromones are important chemical signals in sexual communication, they are traditionally thought to be inactive to larvae. However, it was found that some lepidopteran larvae can be significantly attracted by sex pheromones of the same species in a food context. Here we reported that the host-feeding choice of early-instar Mythimna separata larvae can be effectively regulated by the sex pheromone component (Z)-11-hexadecenal (Z11-16: Ald). Further exploration revealed that two olfactory proteins, M. separata general odorant binding protein 2 (MsGOBP2) and olfactory receptor 3 (MsOR3), were molecular basis of the host-feeding choice regulation mediated by Z11-16: Ald. Silencing either MsGOBP2 or MsOR3 led to a sharply reduced preference for Z11-16: Ald-spiked hosts. It is possible that the Z11-16: Ald-based preference of the M. separata larvae for host is governed by the interplay between MsGOBP2 and MsOR3. In the present research, the interactions between MsGOBP2 and Z11-16: Ald were also discussed using molecular dynamics-based approaches. Our research explored insight into the Z11-16: Ald-mediated host-feeding choice regulation of M. separata larvae, all the results would aid in developing olfaction-based methods for controlling pests in larval stage.
Diversity and Evolution of Computationally Predicted T Cell Epitopes against Human Respiratory Syncytial Virus
Authors: Chen Jiani , Tan Swan , Avadhanula Vasanthi , Moise Leonard , Piedra Pedro A , De Groot Anne S , Bahl Justin 
Published: July 2022

AbstractHuman respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here, we computationally predicted putative T cell epitopes in the Fusion protein (F) and Glycoprotein (G) of RSV wild circulating strains by predicting Major Histocompatibility Complex (MHC) class I and class II binding affinity. We limited our inferences to conserved epitopes in both F and G proteins that have been experimentally validated. We applied multidimensional scaling (MDS) to construct T cell epitope landscapes to investigate the diversity and evolution of T cell profiles across different RSV strains. We find the RSV strains are clustered into three RSV-A groups and two RSV-B groups on this T epitope landscape. These clusters represent divergent RSV strains with potentially different immunogenic profiles. In addition, our results show a greater proportion of F protein T cell epitope content conservation among recent epidemic strains, whereas the G protein T cell epitope content was decreased. Importantly, our results suggest that RSV-A and RSV-B have different patterns of epitope drift and replacement and that RSV-B vaccines may need more frequent updates. Our study provides a novel framework to study RSV T cell epitope evolution. Understanding the patterns of T cell epitope conservation and change may be valuable for vaccine design and assessment.Author SummaryLower respiratory infections caused by human respiratory syncytial virus (RSV) is a global health challenge. B cell epitope immune response has been the major focus of RSV vaccine and therapeutic development. However, T cell epitope induced immunity plays an important role in the resolution of RSV infection. While RSV genetic diversity has been widely reported, few studies focus on RSV T epitope diversity, which can influence vaccine effectiveness. Here, we use computationally predicted T cell epitope profiles of circulating strains to characterize the diversity and evolution of the T cell epitope of RSV A and B. We systematically evaluate the T epitope profile of RSV F and G proteins. We provide a T cell epitope landscape visualization that shows co-circulation of three RSV-A groups and two RSV-B groups, suggesting potentially distinct T cell immunity. Furthermore, our study shows different levels of F and G protein T cell epitope content conservation, which may be important to correlate with duration of vaccine protection. This study provides a novel framework to study RSV T cell epitope evolution, infer RSV T cell immunity at population levels and monitor RSV vaccine effectiveness.