Exosomal DNA: an alternative vehicle for soma-to-germline communication?
J Physiol. 2024 Jan 15. doi: 10.1113/JP286170. Online ahead of print.NO ABSTRACTPMID:38224265 | DOI:10.1113/JP286170 (Source: The Journal of Physiology)
Source: The Journal of Physiology - January 15, 2024 Category: Physiology Authors: Haili Sun Yongsheng Liu Source Type: research
Small peptides: could they have a big role in metabolism and the response to exercise?
J Physiol. 2024 Jan 9. doi: 10.1113/JP283214. Online ahead of print.ABSTRACTExercise is a powerful non-pharmacological intervention for the treatment and prevention of numerous chronic diseases. Contracting skeletal muscles provoke widespread perturbations in numerous cells, tissues and organs, which stimulate multiple integrated adaptations that ultimately contribute to the many health benefits associated with regular exercise. Despite much research, the molecular mechanisms driving such changes are not completely resolved. Technological advancements beginning in the early 1960s have opened new avenues to explore the mech...
Source: The Journal of Physiology - January 10, 2024 Category: Physiology Authors: Muhammed M Atakan İbrahim Türkel Berkay Özerkliğ Şükran N Koşar Dale F Taylor Xu Yan David J Bishop Source Type: research
Pacing intracellular Ca < sup > 2+ < /sup > signals in exocrine acinar cells
J Physiol. 2024 Jan 10. doi: 10.1113/JP284755. Online ahead of print.ABSTRACTAn increase in intracellular [Ca2+ ] in exocrine acinar cells resident in the salivary glands or pancreas is a fundamental event that drives fluid secretion and exocytosis of proteins. Stimulation with secretagogues initiates Ca2+ signals with precise spatiotemporal properties thought to be important for driving physiological output. Both in vitro, in acutely isolated acini, and in vivo, in animals expressing genetically encoded indicators, individual cells appear specialized to initiate Ca2+ signals upon stimulation. Furthermore, these signals ap...
Source: The Journal of Physiology - January 10, 2024 Category: Physiology Authors: David I Yule Takahiro Takano Source Type: research
Small peptides: could they have a big role in metabolism and the response to exercise?
J Physiol. 2024 Jan 9. doi: 10.1113/JP283214. Online ahead of print.ABSTRACTExercise is a powerful non-pharmacological intervention for the treatment and prevention of numerous chronic diseases. Contracting skeletal muscles provoke widespread perturbations in numerous cells, tissues and organs, which stimulate multiple integrated adaptations that ultimately contribute to the many health benefits associated with regular exercise. Despite much research, the molecular mechanisms driving such changes are not completely resolved. Technological advancements beginning in the early 1960s have opened new avenues to explore the mech...
Source: The Journal of Physiology - January 10, 2024 Category: Physiology Authors: Muhammed M Atakan İbrahim Türkel Berkay Özerkliğ Şükran N Koşar Dale F Taylor Xu Yan David J Bishop Source Type: research
Pacing intracellular Ca < sup > 2+ < /sup > signals in exocrine acinar cells
J Physiol. 2024 Jan 10. doi: 10.1113/JP284755. Online ahead of print.ABSTRACTAn increase in intracellular [Ca2+ ] in exocrine acinar cells resident in the salivary glands or pancreas is a fundamental event that drives fluid secretion and exocytosis of proteins. Stimulation with secretagogues initiates Ca2+ signals with precise spatiotemporal properties thought to be important for driving physiological output. Both in vitro, in acutely isolated acini, and in vivo, in animals expressing genetically encoded indicators, individual cells appear specialized to initiate Ca2+ signals upon stimulation. Furthermore, these signals ap...
Source: The Journal of Physiology - January 10, 2024 Category: Physiology Authors: David I Yule Takahiro Takano Source Type: research
Evolutionary feedback from the environment shapes mechanisms that generate genome variation
J Physiol. 2024 Jan 9. doi: 10.1113/JP284411. Online ahead of print.ABSTRACTDarwin recognized that 'a grand and almost untrodden field of inquiry will be opened, on the causes and laws of variation.' However, because the Modern Synthesis assumes that the intrinsic probability of any individual mutation is unrelated to that mutation's potential adaptive value, attention has been focused on selection rather than on the intrinsic generation of variation. Yet many examples illustrate that the term 'random' mutation, as widely understood, is inaccurate. The probabilities of distinct classes of variation are neither evenly distr...
Source: The Journal of Physiology - January 9, 2024 Category: Physiology Authors: Lynn Helena Caporale Source Type: research
Differential effects of mechano-electric feedback mechanisms on whole-heart activation, repolarization, and tension
In conclusion, we found that mechano-electric feedback changes activation and repolarization patterns throughout the heart during sinus rhythm and lead to a markedly more heterogeneous electrophysiological substrate. KEY POINTS: The electrophysiological and mechanical function of the heart are tightly interrelated by excitation-contraction coupling (ECC) in the forward direction and mechano-electric feedback (MEF) in the reverse direction. While ECC is considered in many state-of-the-art computational models of cardiac electromechanics, less is known about the effect of different MEF mechanisms. Accounting for calcium boun...
Source: The Journal of Physiology - January 8, 2024 Category: Physiology Authors: Tobias Gerach Axel Loewe Source Type: research
Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor
In conclusion, S1159F and S1159P are gating variants, which also affect CFTR processing and conduction, but not stability, necessitating the use of combinations of CFTR modulators to optimally restore their channel activity. KEY POINTS: Dysfunction of the ion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes the genetic disease cystic fibrosis (CF). This study investigated two rare pathogenic CFTR variants, S1159F and S1159P, which affect the same amino acid in CFTR, to understand the molecular basis of disease and response to the CFTR-targeted therapy ivacaftor. Both rare variants diminished CFTR f...
Source: The Journal of Physiology - January 8, 2024 Category: Physiology Authors: Hongyu Li Mayuree Rodrat Majid K Al-Salmani Diana-Florentina Veselu Sangwoo T Han Karen S Raraigh Garry R Cutting David N Sheppard Source Type: research
Differential effects of mechano-electric feedback mechanisms on whole-heart activation, repolarization, and tension
In conclusion, we found that mechano-electric feedback changes activation and repolarization patterns throughout the heart during sinus rhythm and lead to a markedly more heterogeneous electrophysiological substrate. KEY POINTS: The electrophysiological and mechanical function of the heart are tightly interrelated by excitation-contraction coupling (ECC) in the forward direction and mechano-electric feedback (MEF) in the reverse direction. While ECC is considered in many state-of-the-art computational models of cardiac electromechanics, less is known about the effect of different MEF mechanisms. Accounting for calcium boun...
Source: The Journal of Physiology - January 8, 2024 Category: Physiology Authors: Tobias Gerach Axel Loewe Source Type: research
Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor
In conclusion, S1159F and S1159P are gating variants, which also affect CFTR processing and conduction, but not stability, necessitating the use of combinations of CFTR modulators to optimally restore their channel activity. KEY POINTS: Dysfunction of the ion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes the genetic disease cystic fibrosis (CF). This study investigated two rare pathogenic CFTR variants, S1159F and S1159P, which affect the same amino acid in CFTR, to understand the molecular basis of disease and response to the CFTR-targeted therapy ivacaftor. Both rare variants diminished CFTR f...
Source: The Journal of Physiology - January 8, 2024 Category: Physiology Authors: Hongyu Li Mayuree Rodrat Majid K Al-Salmani Diana-Florentina Veselu Sangwoo T Han Karen S Raraigh Garry R Cutting David N Sheppard Source Type: research
Mutation protocols share with sexual reproduction the physiological role of producing genetic variation within 'constraints that deconstrain'
J Physiol. 2024 Jan 4. doi: 10.1113/JP285478. Online ahead of print.ABSTRACTBecause the universe of possible DNA sequences is inconceivably vast, organisms have evolved mechanisms for exploring DNA sequence space while substantially reducing the hazard that would otherwise accrue to any process of random, accidental mutation. One such mechanism is meiotic recombination. Although sexual reproduction imposes a seemingly paradoxical 50% cost to fitness, sex evidently prevails because this cost is outweighed by the advantage of equipping offspring with genetic variation to accommodate environmental vicissitudes. The potential ...
Source: The Journal of Physiology - January 5, 2024 Category: Physiology Authors: David G King Source Type: research
Neural coordination of bilateral hand movements: evidence for an involvement of brainstem motor centres
J Physiol. 2024 Jan 4. doi: 10.1113/JP285403. Online ahead of print.ABSTRACTBilateral hand movements are assumed to be coordinated by a neural coupling mechanism. Neural coupling is experimentally reflected in complex electromyographic (EMG) responses in the forearm muscles of both sides to unilateral electrical arm nerve stimulation (ES). The aim of this study was to examine a potential involvement of the reticulospinal system in neural coupling by the application of loud acoustic stimuli (LAS) known to activate neurons of this system. LAS, ES and combined LAS/ES were applied to healthy subjects during visually guided bil...
Source: The Journal of Physiology - January 5, 2024 Category: Physiology Authors: Volker Dietz Nicole Sarah Holliger Andrin Christen Marina Geissmann Linard Filli Source Type: research
Intense exercise at high altitude causes platelet loss across the brain in humans
We examined platelet concentration across the brain in exercising humans at sea level (340 m) and high altitude (6-8 days at 3800 m; a stimulus known to modify platelet function). During intense exercise at sea level, platelet concentration increased similarly by 27 ± 17% in the arterial and internal jugular venous circulations (exercise: P < 0.001, interaction: P = 0.262), indicating no uptake or release of platelets into/from the brain. At high altitude, resting platelet concentrations were similar to sea level values in both the arterial and jugular venous circulations (P = 0.590); however, intense exercise at high ...
Source: The Journal of Physiology - January 5, 2024 Category: Physiology Authors: Travis Dylan Gibbons Hannah G Caldwell Hashim Islam Jennifer Duffy David B MacLeod Philip N Ainslie Source Type: research
Identifying peristaltic pacemaker cells in the upper urinary tract
J Physiol. 2024 Jan 5. doi: 10.1113/JP284754. Online ahead of print.ABSTRACTUrine expulsion from the upper urinary tract is a necessary process that eliminates waste, promotes renal filtration and prevents nephron damage. To facilitate the movement of urine boluses throughout the upper urinary tract, smooth muscle cells that line the renal pelvis contract in a coordinated effort to form peristaltic waves. Resident pacemaker cells in the renal pelvis are critical to this process and spontaneously evoke transient depolarizations that initiate each peristaltic wave and establish rhythmic contractions. Renal pacemakers have be...
Source: The Journal of Physiology - January 5, 2024 Category: Physiology Authors: Nathan Grainger Source Type: research
Mutation protocols share with sexual reproduction the physiological role of producing genetic variation within 'constraints that deconstrain'
J Physiol. 2024 Jan 4. doi: 10.1113/JP285478. Online ahead of print.ABSTRACTBecause the universe of possible DNA sequences is inconceivably vast, organisms have evolved mechanisms for exploring DNA sequence space while substantially reducing the hazard that would otherwise accrue to any process of random, accidental mutation. One such mechanism is meiotic recombination. Although sexual reproduction imposes a seemingly paradoxical 50% cost to fitness, sex evidently prevails because this cost is outweighed by the advantage of equipping offspring with genetic variation to accommodate environmental vicissitudes. The potential ...
Source: The Journal of Physiology - January 5, 2024 Category: Physiology Authors: David G King Source Type: research
