IF 6.4 1区生物学

eLife Pub Date : 2024-08-30 DOI: 10.7554/eLife.85742

Ikhwan Bin Khalid, Eric T Reifenstein, Naomi Auer, Lukas Kunz, Richard Kempter

{"title":"Quantitative modeling of the emergence of macroscopic grid-like representations.","authors":"Ikhwan Bin Khalid, Eric T Reifenstein, Naomi Auer, Lukas Kunz, Richard Kempter","doi":"10.7554/eLife.85742","DOIUrl":"https://doi.org/10.7554/eLife.85742","url":null,"abstract":"When subjects navigate through spatial environments, grid cells exhibit firing fields that are arranged in a triangular grid pattern. Direct recordings of grid cells from the human brain are rare. Hence, functional magnetic resonance imaging (fMRI) studies proposed an indirect measure of entorhinal grid-cell activity, quantified as hexadirectional modulation of fMRI activity as a function of the subject's movement direction. However, it remains unclear how the activity of a population of grid cells may exhibit hexadirectional modulation. Here, we use numerical simulations and analytical calculations to suggest that this hexadirectional modulation is best explained by head-direction tuning aligned to the grid axes, whereas it is not clearly supported by a bias of grid cells toward a particular phase offset. Firing-rate adaptation can result in hexadirectional modulation, but the available cellular data is insufficient to clearly support or refute this option. The magnitude of hexadirectional modulation furthermore depends considerably on the subject's navigation pattern, indicating that future fMRI studies could be designed to test which hypothesis most likely accounts for the fMRI measure of grid cells. Our findings also underline the importance of quantifying the properties of human grid cells to further elucidate how hexadirectional modulations of fMRI activity may emerge.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adverse impact of female reproductive signaling on age-dependent neurodegeneration after mild head trauma in Drosophila. 雌性生殖信号对果蝇头部轻微创伤后年龄依赖性神经变性的不利影响

IF 6.4 1区生物学

eLife Pub Date : 2024-08-30 DOI: 10.7554/eLife.97908

Changtian Ye, Ryan Ho, Kenneth H Moberg, James Q Zheng

{"title":"Adverse impact of female reproductive signaling on age-dependent neurodegeneration after mild head trauma in Drosophila.","authors":"Changtian Ye, Ryan Ho, Kenneth H Moberg, James Q Zheng","doi":"10.7554/eLife.97908","DOIUrl":"https://doi.org/10.7554/eLife.97908","url":null,"abstract":"Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative deficits, nor do we know how sex and age compound the outcome. Using a Drosophila model, we demonstrate that exposure to mild head trauma causes neurodegenerative conditions that emerge late in life and disproportionately affect females. Increasing age-at-injury further exacerbates this effect in a sexually dimorphic manner. We further identify sex peptide signaling as a key factor in female susceptibility to post-injury brain deficits. RNA sequencing highlights a reduction in innate immune defense transcripts specifically in mated females during late life. Our findings establish a causal relationship between early head trauma and late-life neurodegeneration, emphasizing sex differences in injury response and the impact of age-at-injury. Finally, our findings reveal that reproductive signaling adversely impacts female response to mild head insults and elevates vulnerability to late-life neurodegeneration.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coping with salt stress. 应对盐压力。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-30 DOI: 10.7554/eLife.101732

Xiaoyan Liang, Caifu Jiang

引用次数: 0

Polysaccharides induce deep-sea Lentisphaerae strains to release chronic bacteriophages. 多糖诱导深海扁形目菌株释放慢性噬菌体。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-29 DOI: 10.7554/eLife.92345

Chong Wang, Rikuan Zheng, Tianhang Zhang, Chaomin Sun

引用次数: 0

Damage-induced basal epithelial cell migration modulates the spatial organization of redox signaling and sensory neuron regeneration. 损伤诱导的基底上皮细胞迁移可调节氧化还原信号传导和感觉神经元再生的空间组织。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-29 DOI: 10.7554/eLife.94995

Alexandra M Fister, Adam Horn, Michael R Lasarev, Anna Huttenlocher

引用次数: 0

Detection of TurboID fusion proteins by fluorescent streptavidin outcompetes antibody signals and visualises targets not accessible to antibodies. 用荧光链霉亲和素检测 TurboID 融合蛋白可胜过抗体信号，并可观察到抗体无法触及的目标。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-29 DOI: 10.7554/eLife.95028

Johanna Odenwald, Bernardo Gabiatti, Silke Braune, Siqi Shen, Martin Zoltner, Susanne Kramer

{"title":"Detection of TurboID fusion proteins by fluorescent streptavidin outcompetes antibody signals and visualises targets not accessible to antibodies.","authors":"Johanna Odenwald, Bernardo Gabiatti, Silke Braune, Siqi Shen, Martin Zoltner, Susanne Kramer","doi":"10.7554/eLife.95028","DOIUrl":"10.7554/eLife.95028","url":null,"abstract":"Immunofluorescence localises proteins via fluorophore-labelled antibodies. However, some proteins evade detection due to antibody-accessibility issues or because they are naturally low abundant or antigen density is reduced by the imaging method. Here, we show that the fusion of the target protein to the biotin ligase TurboID and subsequent detection of biotinylation by fluorescent streptavidin offers an 'all in one' solution to these restrictions. For all proteins tested, the streptavidin signal was significantly stronger than an antibody signal, markedly improving the sensitivity of expansion microscopy and correlative light and electron microscopy. Importantly, proteins within phase-separated regions, such as the central channel of the nuclear pores, the nucleolus, or RNA granules, were readily detected with streptavidin, while most antibodies failed. When TurboID is used in tandem with an HA epitope tag, co-probing with streptavidin and anti-HA can map antibody-accessibility and we created such a map for the trypanosome nuclear pore. Lastly, we show that streptavidin imaging resolves dynamic, temporally, and spatially distinct sub-complexes and, in specific cases, reveals a history of dynamic protein interaction. In conclusion, streptavidin imaging has major advantages for the detection of lowly abundant or inaccessible proteins and in addition, provides information on protein interactions and biophysical environment.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Divergent downstream biosynthetic pathways are supported by L-cysteine synthases of Mycobacterium tuberculosis. 结核分枝杆菌的 L-半胱氨酸合成酶支持不同的下游生物合成途径。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-29 DOI: 10.7554/eLife.91970

Mehak Zahoor Khan, Debbie M Hunt, Biplab Singha, Yogita Kapoor, Nitesh Kumar Singh, D V Sai Prasad, Sriram Dharmarajan, Divya Tej Sowpati, Luiz Pedro S de Carvalho, Vinay Kumar Nandicoori

{"title":"Divergent downstream biosynthetic pathways are supported by <sc>L</sc>-cysteine synthases of Mycobacterium tuberculosis.","authors":"Mehak Zahoor Khan, Debbie M Hunt, Biplab Singha, Yogita Kapoor, Nitesh Kumar Singh, D V Sai Prasad, Sriram Dharmarajan, Divya Tej Sowpati, Luiz Pedro S de Carvalho, Vinay Kumar Nandicoori","doi":"10.7554/eLife.91970","DOIUrl":"10.7554/eLife.91970","url":null,"abstract":"Mycobacterium tuberculosis's (Mtb) autarkic lifestyle within the host involves rewiring its transcriptional networks to combat host-induced stresses. With the help of RNA sequencing performed under various stress conditions, we identified that genes belonging to Mtb sulfur metabolism pathways are significantly upregulated during oxidative stress. Using an integrated approach of microbial genetics, transcriptomics, metabolomics, animal experiments, chemical inhibition, and rescue studies, we investigated the biological role of non-canonical L-cysteine synthases, CysM and CysK2. While transcriptome signatures of RvΔcysM and RvΔcysK2 appear similar under regular growth conditions, we observed unique transcriptional signatures when subjected to oxidative stress. We followed pool size and labelling (34S) of key downstream metabolites, viz. mycothiol and ergothioneine, to monitor L-cysteine biosynthesis and utilization. This revealed the significant role of distinct L-cysteine biosynthetic routes on redox stress and homeostasis. CysM and CysK2 independently facilitate Mtb survival by alleviating host-induced redox stress, suggesting they are not fully redundant during infection. With the help of genetic mutants and chemical inhibitors, we show that CysM and CysK2 serve as unique, attractive targets for adjunct therapy to combat mycobacterial infection.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis. TRIP13 定位于突触染色体，是减数分裂的剂量敏感调节因子。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-29 DOI: 10.7554/eLife.92195

Jessica Y Chotiner, N Adrian Leu, Fang Yang, Isabella G Cossu, Yongjuan Guan, Huijuan Lin, P Jeremy Wang

{"title":"TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis.","authors":"Jessica Y Chotiner, N Adrian Leu, Fang Yang, Isabella G Cossu, Yongjuan Guan, Huijuan Lin, P Jeremy Wang","doi":"10.7554/eLife.92195","DOIUrl":"10.7554/eLife.92195","url":null,"abstract":"Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. Mouse TRIP13 and its ortholog Pch2 are instrumental in remodeling HORMA domain proteins. HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed homologs. Here we report that TRIP13 localizes to the synapsed SC in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. Loss of TRIP13 leads to meiotic arrest and thus sterility in both sexes. Trip13-null meiocytes exhibit abnormal persistence of HORMAD1 and HOMRAD2 on synapsed SC and chromosome asynapsis that preferentially affects XY and centromeric ends. These major phenotypes are consistent with reported phenotypes of Trip13 hypomorph alleles. Trip13 heterozygous mice exhibit meiotic defects that are less severe than the Trip13-null mice, showing that TRIP13 is a dosage-sensitive regulator of meiosis. Localization of TRIP13 to the synapsed SC is independent of SC axial element proteins such as REC8 and SYCP2/SYCP3. Terminal FLAG-tagged TRIP13 proteins are functional and recapitulate the localization of native TRIP13 to SC and telomeres. Therefore, the evolutionarily conserved localization of TRIP13/Pch2 to the synapsed chromosomes provides an explanation for dissociation of HORMA domain proteins upon synapsis in diverse organisms.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Opposing actions of co-released GABA and neurotensin on the activity of preoptic neurons and on body temperature. 共同释放的 GABA 和神经紧张素对视前神经元的活动和体温有相反的作用。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-29 DOI: 10.7554/eLife.98677

Iustin V Tabarean

{"title":"Opposing actions of co-released GABA and neurotensin on the activity of preoptic neurons and on body temperature.","authors":"Iustin V Tabarean","doi":"10.7554/eLife.98677","DOIUrl":"10.7554/eLife.98677","url":null,"abstract":"Neurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial preoptic area, a region that plays an important role in the control of thermoregulation, contains a high density of neurotensinergic neurons and Nts receptors. The conditions in which neurotensinergic neurons play a role in thermoregulation are not known. In this study, optogenetic stimulation of preoptic Nts neurons induced a small hyperthermia. In vitro, optogenetic stimulation of preoptic Nts neurons resulted in synaptic release of GABA and net inhibition of the preoptic pituitary adenylate cyclase-activating polypeptide (Adcyap1) neurons firing activity. GABA-A receptor antagonist or genetic deletion of Slc32a1 (VGAT) in Nts neurons unmasked also an excitatory effect that was blocked by a Nts receptor 1 antagonist. Stimulation of preoptic Nts neurons lacking Slc32a1 resulted in excitation of Adcyap1 neurons and hypothermia. Mice lacking Slc32a1 expression in Nts neurons presented changes in the fever response and in the responses to heat or cold exposure as well as an altered circadian rhythm of body temperature. Chemogenetic activation of all Nts neurons in the brain induced a 4-5°C hypothermia, which could be blocked by Nts receptor antagonists in the preoptic area. Chemogenetic activation of preoptic neurotensinergic projections resulted in robust excitation of preoptic Adcyap1 neurons. Taken together, our data demonstrate that endogenously released Nts can induce potent hypothermia and that excitation of preoptic Adcyap1 neurons is the cellular mechanism that triggers this response.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential increase of hippocampal subfield volume after socio-affective mental training relates to reductions in diurnal cortisol. 社会情感心理训练后海马区体积的不同程度增加与昼夜皮质醇的减少有关。

IF 6.4 1区生物学

eLife Pub Date : 2024-08-28 DOI: 10.7554/eLife.87634

Sofie Louise Valk, Veronika Engert, Lara Puhlmann, Roman Linz, Benoit Caldairou, Andrea Bernasconi, Neda Bernasconi, Boris C Bernhardt, Tania Singer

{"title":"Differential increase of hippocampal subfield volume after socio-affective mental training relates to reductions in diurnal cortisol.","authors":"Sofie Louise Valk, Veronika Engert, Lara Puhlmann, Roman Linz, Benoit Caldairou, Andrea Bernasconi, Neda Bernasconi, Boris C Bernhardt, Tania Singer","doi":"10.7554/eLife.87634","DOIUrl":"10.7554/eLife.87634","url":null,"abstract":"The hippocampus is a central modulator of the HPA-axis, impacting the regulation of stress on brain structure, function, and behavior. The current study assessed whether three different types of 3 months mental Training Modules geared towards nurturing (a) attention-based mindfulness, (b) socio-affective, or (c) socio-cognitive skills may impact hippocampal organization by reducing stress. We evaluated mental training-induced changes in hippocampal subfield volume and intrinsic functional connectivity, by combining longitudinal structural and resting-state fMRI connectivity analysis in 332 healthy adults. We related these changes to changes in diurnal and chronic cortisol levels. We observed increases in bilateral cornu ammonis volume (CA1-3) following the 3 months compassion-based module targeting socio-affective skills (Affect module), as compared to socio-cognitive skills (Perspective module) or a waitlist cohort with no training intervention. Structural changes were paralleled by relative increases in functional connectivity of CA1-3 when fostering socio-affective as compared to socio-cognitive skills. Furthermore, training-induced changes in CA1-3 structure and function consistently correlated with reductions in cortisol output. Notably, using a multivariate approach, we found that other subfields that did not show group-level changes also contributed to changes in cortisol levels. Overall, we provide a link between a socio-emotional behavioural intervention, changes in hippocampal subfield structure and function, and reductions in cortisol in healthy adults.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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