Inbreeding negatively affects various life-history traits, with inbred individuals typically having lower fit- ness than outbred individuals （=inbreeding depression）. Inbreeding depression is often emphasized under ...Inbreeding negatively affects various life-history traits, with inbred individuals typically having lower fit- ness than outbred individuals （=inbreeding depression）. Inbreeding depression is often emphasized under environmental stress, but the underlying mechanisms and potential long-lasting consequences of such inbreeding-environment interactions remain poorly understood. Here, we hypothesize that inbreeding-environment interactions that occur early in life have long-term physiological effects, in partic- ular on the adult oxidative balance. We applied a unique experimental design to manipulate early life conditions of inbred and outbred songbirds （Serinus canaria） that allowed us to separate prenatal and postnatal components of early life conditions and their respective importance in inbreeding-environment interactions. We measured a wide variety of markers of oxidative status in adulthood, resulting in a com- prehensive account for oxidative balance. Using a Bayesian approach with Markov chain Monte Carlo, we found clear sex-specific effects and we also found only in females small yet significant long-term effects of inbreeding-environment interactions on adult oxidative balance. Postnatal components of early life conditions were most persuasively reflected on adult oxidative balance, with inbred females that experienced disadvantageous postnatal conditions upregulating enzymatic antioxidants in adulthood. Our study provides some evidence that adult oxidative balance can reflect inbreeding-environment inter- actions early in life, but given the rather small effects that were limited to females, we conclude that oxida- tive stress miaht have a limited role as mechanism underlvina inhre.e.dina-envirnnme.nt inte.raetinn.q_展开更多
Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the ma...Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix（ECM）microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide（PA）gels can lead to different density of ECM ancho-展开更多
Growing evidence suggests that oxidative stress is a major cause of male infertility.Spermatozoa are highly sensitive cells due to the vulnerability of their membrane fatty acids and the diminished antioxidant defense...Growing evidence suggests that oxidative stress is a major cause of male infertility.Spermatozoa are highly sensitive cells due to the vulnerability of their membrane fatty acids and the diminished antioxidant defense.Reactive oxygen species(ROS)impact multiple signaling pathways involved in mitochondrial dysfunction,hormonal unbalance and semen quality decline.The origin of ROS is diverse,including generated normal cellular metabolism,environmental exposure,advanced paternal age and inflammation.Research has indicated that antioxidant supplementation can improve oxidative stress and reduce the risk of chronic diseases.Moreover,it is widely known that antioxidant supplementation can enhance sperm quality and increase the pregnancy rate in couples undergoing fertility treatments.The current study highlights the deleterious effect of ROS and its impact on semen function.In addition,it contributes to the development of a clinical approach for the use of antioxidants in the management of male infertility.展开更多
Dear Editor,Recombinant protein therapeutics and gene therapies can help rescue monogenic disease phenotypes(Ebrahimi and Samanta,2023).Sufficient/high expression of a therapeutic product is an important consideration...Dear Editor,Recombinant protein therapeutics and gene therapies can help rescue monogenic disease phenotypes(Ebrahimi and Samanta,2023).Sufficient/high expression of a therapeutic product is an important consideration in this regard,which is usually achieved by gene redesign,focused on altering synonymous codon usage/codon context,aimed at enhancing translational rates(Alexaki et al.,2019).Different approaches exist to adjust synonymous codon usage and boost protein expression levels(Katneni et al.,2022).As these strategies do not alter the primary sequence of a protein(Liu et al.,2021)they are not expected to alter protein structure and function.However。展开更多
Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to re...Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to resume aggressive growth, and eventually become overt bone metastases. Recent studies have begun to shed light on this complicated process and revealed multiple steps and intermediate states of colonizing DTCs. However, how cancer-host interactions evolve during this process needs to be further understood. Most of our current knowledge of the bone microenvironment is obtained through studies looking for the hematopoietic stem cell(HSC) niche. Although this long-standing question has not yet been resolved, our search for the HSC niche has resulted in a detailed map of various cell types in the bone marrow. Furthermore, various techniques used to find the HSC niche may also be adapted for finding the cancer cell niche. In this article, we will review the recent progress in both the DTC and HSC areas with a focus on their potential microenvironment niches. We will also discuss how to apply what we have learned from HSC studies to map DTCs in the bone context. We hope to stimulate thoughts and ideas to further elucidate the bone colonization process, and develop potential therapeutic interventions.展开更多
The synthesis of stable open-shell hydrocarbon system comprising of pentagon defects and zigzag edges remains unexplored,which can be considered as model compounds for unraveling the spin-localized states in graphene ...The synthesis of stable open-shell hydrocarbon system comprising of pentagon defects and zigzag edges remains unexplored,which can be considered as model compounds for unraveling the spin-localized states in graphene edges.With concise synthetic approaches,twoπ-extended fluorenyl radicals were synthesized and isolated in their crystalline state.X-ray crystallographic analysis and studies on the magnetic,optical and electrochemical properties of neutral and charged species have revealed an interesting edge-dependence of the spin/charge distribution,that is,the spin and charge distribution shifted from the pentagon defects to the zigzag edges with the elongation of conjugation.Such phenomenon was unprecedented for hydrocarbon radicals and can be rationalized by the recovery of Clar Sextets in the dominant resonance structures.Remarkably,one of the radicals exhibited exceptional stability in air-saturated solutions with the half-life time up to 260 d,thus providing opportunities for the applications as electronic materials.展开更多
Computational biology methods are now firmly entrenched in the drug discovery process.These methods focus on modeling and simulations of biological systems to complement and direct conventional experimental approaches...Computational biology methods are now firmly entrenched in the drug discovery process.These methods focus on modeling and simulations of biological systems to complement and direct conventional experimental approaches.Two important branches of computational biology include protein homology modeling and the computational biophysics method of molecular dynamics.Protein modeling methods attempt to accurately predict three-dimensional(3D)structures of uncrystallized proteins for subsequent structure-based drug design applications.Molecular dynamics methods aim to elucidate the molecular motions of the static representations of crystallized protein structures.In this review we highlight recent novel methodologies in the field of homology modeling and molecular dynamics.Selected drug discovery applications using these methods conclude the review.展开更多
Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA...Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA is long non-protein coding RNA(lncRNA).Besides their aforementioned roles in cancer cell biology,dysregulation of lncRNAs contribute to resistance to therapeutic treatments.A couple of important therapeutic classes are chemotherapy and targeted/hormone therapies.This review highlights the variety of malignancies affected by lncRNA dysregulation and the underlying mechanism causing therapeutic resistance.展开更多
文摘Inbreeding negatively affects various life-history traits, with inbred individuals typically having lower fit- ness than outbred individuals （=inbreeding depression）. Inbreeding depression is often emphasized under environmental stress, but the underlying mechanisms and potential long-lasting consequences of such inbreeding-environment interactions remain poorly understood. Here, we hypothesize that inbreeding-environment interactions that occur early in life have long-term physiological effects, in partic- ular on the adult oxidative balance. We applied a unique experimental design to manipulate early life conditions of inbred and outbred songbirds （Serinus canaria） that allowed us to separate prenatal and postnatal components of early life conditions and their respective importance in inbreeding-environment interactions. We measured a wide variety of markers of oxidative status in adulthood, resulting in a com- prehensive account for oxidative balance. Using a Bayesian approach with Markov chain Monte Carlo, we found clear sex-specific effects and we also found only in females small yet significant long-term effects of inbreeding-environment interactions on adult oxidative balance. Postnatal components of early life conditions were most persuasively reflected on adult oxidative balance, with inbred females that experienced disadvantageous postnatal conditions upregulating enzymatic antioxidants in adulthood. Our study provides some evidence that adult oxidative balance can reflect inbreeding-environment inter- actions early in life, but given the rather small effects that were limited to females, we conclude that oxida- tive stress miaht have a limited role as mechanism underlvina inhre.e.dina-envirnnme.nt inte.raetinn.q_
基金supported in part by NIH HL098472NSF CBET0846429
文摘Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix（ECM）microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide（PA）gels can lead to different density of ECM ancho-
文摘Growing evidence suggests that oxidative stress is a major cause of male infertility.Spermatozoa are highly sensitive cells due to the vulnerability of their membrane fatty acids and the diminished antioxidant defense.Reactive oxygen species(ROS)impact multiple signaling pathways involved in mitochondrial dysfunction,hormonal unbalance and semen quality decline.The origin of ROS is diverse,including generated normal cellular metabolism,environmental exposure,advanced paternal age and inflammation.Research has indicated that antioxidant supplementation can improve oxidative stress and reduce the risk of chronic diseases.Moreover,it is widely known that antioxidant supplementation can enhance sperm quality and increase the pregnancy rate in couples undergoing fertility treatments.The current study highlights the deleterious effect of ROS and its impact on semen function.In addition,it contributes to the development of a clinical approach for the use of antioxidants in the management of male infertility.
基金supported by grant R01HL151392(to A.A.K)and AMED-CREST with Grant Number JP21gm1410008(to H.T.)supported by funds from the Center for Biologics Evaluation and Research,US Food and Drug Administration.
文摘Dear Editor,Recombinant protein therapeutics and gene therapies can help rescue monogenic disease phenotypes(Ebrahimi and Samanta,2023).Sufficient/high expression of a therapeutic product is an important consideration in this regard,which is usually achieved by gene redesign,focused on altering synonymous codon usage/codon context,aimed at enhancing translational rates(Alexaki et al.,2019).Different approaches exist to adjust synonymous codon usage and boost protein expression levels(Katneni et al.,2022).As these strategies do not alter the primary sequence of a protein(Liu et al.,2021)they are not expected to alter protein structure and function.However。
基金supported by the US Department of Defense DAMD W81XWH-16-1-0073 (Era of Hope Scholarship), NCI CA183878Breast Cancer Research Foundation, Susan G. Komen CCR14298445McNair Medical Institute
文摘Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to resume aggressive growth, and eventually become overt bone metastases. Recent studies have begun to shed light on this complicated process and revealed multiple steps and intermediate states of colonizing DTCs. However, how cancer-host interactions evolve during this process needs to be further understood. Most of our current knowledge of the bone microenvironment is obtained through studies looking for the hematopoietic stem cell(HSC) niche. Although this long-standing question has not yet been resolved, our search for the HSC niche has resulted in a detailed map of various cell types in the bone marrow. Furthermore, various techniques used to find the HSC niche may also be adapted for finding the cancer cell niche. In this article, we will review the recent progress in both the DTC and HSC areas with a focus on their potential microenvironment niches. We will also discuss how to apply what we have learned from HSC studies to map DTCs in the bone context. We hope to stimulate thoughts and ideas to further elucidate the bone colonization process, and develop potential therapeutic interventions.
基金support from the National Natural Science Foundation of China(Grant No.21971187)the Natural ScienceFoundationof Tianjin(19JCJQJC62700)the Haihe Laboratory of Sustainable Chemical Transformations。
文摘The synthesis of stable open-shell hydrocarbon system comprising of pentagon defects and zigzag edges remains unexplored,which can be considered as model compounds for unraveling the spin-localized states in graphene edges.With concise synthetic approaches,twoπ-extended fluorenyl radicals were synthesized and isolated in their crystalline state.X-ray crystallographic analysis and studies on the magnetic,optical and electrochemical properties of neutral and charged species have revealed an interesting edge-dependence of the spin/charge distribution,that is,the spin and charge distribution shifted from the pentagon defects to the zigzag edges with the elongation of conjugation.Such phenomenon was unprecedented for hydrocarbon radicals and can be rationalized by the recovery of Clar Sextets in the dominant resonance structures.Remarkably,one of the radicals exhibited exceptional stability in air-saturated solutions with the half-life time up to 260 d,thus providing opportunities for the applications as electronic materials.
基金the US Department of Defense Concept Awards(BC085871)US National Institute of Health P41 grant(5P41GM079588-03)+1 种基金Grant#IRG-08-061-01 from the American Cancer Society to SZSSP was supported by UTHealth Innovation for Cancer Prevention Research Pre-doctoral Fellowship,The University of Texas School of Public Health-Cancer Prevention and Research Institute of Texas grant#RP101503.
文摘Computational biology methods are now firmly entrenched in the drug discovery process.These methods focus on modeling and simulations of biological systems to complement and direct conventional experimental approaches.Two important branches of computational biology include protein homology modeling and the computational biophysics method of molecular dynamics.Protein modeling methods attempt to accurately predict three-dimensional(3D)structures of uncrystallized proteins for subsequent structure-based drug design applications.Molecular dynamics methods aim to elucidate the molecular motions of the static representations of crystallized protein structures.In this review we highlight recent novel methodologies in the field of homology modeling and molecular dynamics.Selected drug discovery applications using these methods conclude the review.
基金This work was supported by Baylor College of Medicine Comprehensive Cancer Training Program(CPRIT RP160283).
文摘Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA is long non-protein coding RNA(lncRNA).Besides their aforementioned roles in cancer cell biology,dysregulation of lncRNAs contribute to resistance to therapeutic treatments.A couple of important therapeutic classes are chemotherapy and targeted/hormone therapies.This review highlights the variety of malignancies affected by lncRNA dysregulation and the underlying mechanism causing therapeutic resistance.
