Structural Connectivity Remote From Lesions Correlates With Somatosensory Outcome Poststroke.

Background and Purpose: Changes in connectivity of white matter fibers remote to a stroke lesion, suggestive of structural connectional diaschisis, may impact on clinical impairment and recovery after stroke. However, until recently, we have not had tract-specific techniques to map changes in white matter tracts in vivo in humans to enable investigation of potential mechanisms and clinical impact of such remote changes. Our aim was to identify and quantify white matter tracts that are affected remote from a stroke lesion and to investigate the associations between reductions in tract-specific connectivity and impaired touch discrimination function after stroke. Methods: We applied fixel-based analysis to diffusion magnetic resonance imaging data from 37 patients with stroke (right lesion =16; left lesion =21) and 26 age-matched healthy adults. Three quantitative metrics were compared between groups: fiber density; fiber-bundle cross-section; and a combined measure of both (fiber-bundle cross-section) that reflects axonal structural connectivity. Results: Compared with healthy adults, patients with stroke showed significant common fiber-bundle cross-section and fiber density reductions in 4 regions remote from focal lesions that play roles in somatosensory and spatial information processing. Structural connectivity along the somatosensory fibers of the lesioned hemisphere was correlated with contralesional hand touch function. Touch function of the ipsilesional hand was associated with connectivity of the superior longitudinal fasciculus, and, for the right-lesion group, the corpus callosum. Conclusions: Remote tract-specific reductions in axonal connectivity indicated by diffusion imaging measures are observed in the somatosensory network after stroke. These remote white matter connectivity reductions, indicative of structural connectional diaschisis, are associated with touch impairment in patients with stroke.

Normal Pressure Hydrocephalus Associated with Alzheimer's Disease.

OBJECTIVE: The aim was to investigate whether neurodegenerative biomarkers in cerebrospinal fluid (CSF) differentiate patients with suspected normal pressure hydrocephalus (NPH) who respond to CSF drainage from patients who do not respond. METHODS: Data from 62 consecutive patients who presented with magnetic resonance imaging changes indicative of NPH were studied with regard to cognitive and gait functions before and after drainage of 40-50ml of CSF. Additionally, S100 protein, neuron-specific enolase, ß-amyloid protein, tau protein and phospho-tau were determined in CSF. Statistical analyses were carried out with ANOVA and multiple linear regression. RESULTS: Patients with CSF constellations typical for Alzheimer's disease (n = 28) improved significantly in cognitive and gait-related functions after CSF drainage. In contrast, those patients without a CSF constellation typical for Alzheimer's disease (n = 34) did not improve in cognitive and gait-related functions after CSF drainage. In addition, positive CSF biomarkers for Alzheimer's disease predicted these improvements. INTERPRETATION: Our data suggest an association between Alzheimer's disease and NPH changes, supporting the recently suggested dichotomy of a neurodegenerative NPH and a true idiopathic NPH, with the latter appearing to be rare. ANN NEUROL 2020;88:703-711.

Belief formation - A driving force for brain evolution.

The topic of belief has been neglected in the natural sciences for a long period of time. Recent neuroscience research in non-human primates and humans, however, has shown that beliefs are the neuropsychic product of fundamental brain processes that attribute affective meaning to concrete objects and events, enabling individual goal setting, decision making and maneuvering in the environment. With regard to the involved neural processes they can be categorized as empirical, relational, and conceptual beliefs. Empirical beliefs are about objects and relational beliefs are about events as in tool use and in interactions between subjects that develop below the level of awareness and are up-dated dynamically. Conceptual beliefs are more complex being based on narratives and participation in ritual acts. As neural processes are known to require computational space in the brain, the formation of inceasingly complex beliefs demands extra neural resources. Here, we argue that the evolution of human beliefs is related to the phylogenetic enlargement of the brain including the parietal and medial frontal cortex in humans.

Reduced gray matter volume in the left prefrontal, occipital, and temporal regions as predictors for posttraumatic stress disorder: a voxel-based morphometric study.

The concept of acute stress disorder (ASD) was introduced as a diagnostic entity to improve the identification of traumatized people who are likely to develop posttraumatic stress disorder (PTSD). Neuroanatomical models suggest that changes in the prefrontal cortex, amygdala, and hippocampus play a role in the development of PTSD. Using voxel-based morphometry, this study aimed to investigate the predictive power of gray matter volume (GMV) alterations for developing PTSD. The GMVs of ASD patients (n = 21) were compared to those of PTSD patients (n = 17) and healthy controls (n = 18) in whole-brain and region-of-interest analyses. The GMV alterations seen in ASD patients shortly after the traumatic event (T1) were also correlated with PTSD symptom severity and symptom clusters 4 weeks later (T2). Compared with healthy controls, the ASD patients had significantly reduced GMV in the left visual cortex shortly after the traumatic event (T1) and in the left occipital and prefrontal regions 4 weeks later (T2); no significant differences in GMV were seen between the ASD and PTSD patients. Furthermore, a significant negative association was found between the GMV reduction in the left lateral temporal regions seen after the traumatic event (T1) and PTSD hyperarousal symptoms 4 weeks later (T2). Neither amygdala nor hippocampus alterations were predictive for the development of PTSD. These data suggest that gray matter deficiencies in the left hemispheric occipital and temporal regions in ASD patients may predict a liability for developing PTSD.

Increased early mortality and morbidity after total hip arthroplasty in patients with socioeconomic disadvantage: a report from the Swedish Hip Arthroplasty Register.

Background and purpose - Socioeconomic status is associated with the outcome of major surgery. We investigated the association of socioeconomic status with the risk of early mortality and readmissions after primary total hip arthroplasty (THA). Patients and methods - We obtained information on income, education, immigration, and cohabiting status as well as comorbidities of 166,076 patients who underwent primary THA due to primary osteoarthritis (OA) from the Swedish Hip Arthroplasty Register, the Swedish National Inpatient Register and Statistics Sweden. Multivariable Cox regression models were fitted to estimate the adjusted risk of mortality or readmissions within 90 days after index surgery. Results - Compared with patients on a low income, the adjusted risk of 30-day mortality was considerably lower in patients on a high income (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.7) and in those on a medium income (HR 0.7, CI 0.6-0.9). Similar risk reductions were found for the endpoint 90-day mortality. Patients with a high income had a lower adjusted risk of readmission for cardiovascular reasons than those with a low income (HR 0.7, CI 0.6-0.9), as had those with a higher level of education (adjusted HR 0.7, CI 0.6-0.9). Patients with higher socioeconomic status had a lower degree of comorbidities than socioeconomically disadvantaged patients. However, adjusting for socioeconomic confounders in multivariable models only marginally influenced the predictive ability of the models, as expressed by their area under the curve. Interpretation - Income and level of education are strongly associated with early mortality and readmissions after primary THA, and both parameters are closely connected to health status. Since adjustment for socioeconomic confounders only marginally improved the predictive ability of multivariable regression models our findings indicate that comorbidities may under certain circumstances serve as an acceptable proxy measure of socioeconomic background.

Sequence of 305,996 total hip and knee arthroplasties in patients undergoing operations on more than 1 joint.

Background and purpose - Patient-specific data on multiple total arthroplasties (TA) of the lower limbs due to osteoarthritis (OA) are limited. We investigated the sequence of surgical procedures and risk factors for additional surgery in such patients. Patients and methods - 305,996 patients operated with a TA of the hip and/or knee due to OA were extracted from the Swedish National Hip (SHAR) and the Swedish Knee Arthroplasty Register (SKAR). 177,834 total hip arthroplasty (THA, 56% women, mean age 69 years) and 128,162 total knee arthroplasty (TKA, 60% women, mean age 69 years) procedures constituted the index operations. The mean, median, and maximum follow-up was 8, 6, and 23 years. Multivariable Cox regression analysis was used and Kaplan-Meier survival curves were constructed. Results - Right-sided primary TA (34%) was most frequent. Subsequent surgery was most frequent after primary left-sided TKA (33%). The time interval to a second TA procedure was 3.1 (SD 3.2) years after TKA and 4.0 (SD 3.9) years after THA. After the index TA the probability of no subsequent surgery amounted to 64% (SD 0.3) for THA and 58% (SD 0.4) for TKA over 20 years. Lower age, female sex, left side, and TKA at index operation were associated with a higher probability for subsequent TA. Interpretation - Delineation of factors that influence risk and the size of the risk for subsequent TA in 1 of the 3 major remaining joints is of value for clinicians and healthcare providers in the decision-making process for future resource allocation.

From Believing to Belief: A General Theoretical Model.

Cognitive neuroscience research has begun to explore the mental processes underlying what a belief and what believing are. Recent evidence suggests that believing involves fundamental brain functions that result in meaningful probabilistic representations, called beliefs. When relatively stable, these beliefs allow for guidance of behavior in individuals and social groups. However, they are also fluid and can be modified by new relevant information, interpersonal contact, social pressure, and situational demands. We present a theoretical model of believing that can account for the formation of both empirically grounded and metaphysical beliefs.

The transcriptomic and proteomic responses of Daphnia pulex to changes in temperature and food supply comprise environment-specific and clone-specific elements.

BACKGROUND: Regulatory adjustments to acute and chronic temperature changes are highly important for aquatic ectotherms because temperature affects their metabolic rate as well as the already low oxygen concentration in water, which can upset their energy balance. This also applies to severe changes in food supply. Thus, we studied on a molecular level (transcriptomics and/or proteomics) the immediate responses to heat stress and starvation and the acclimation to different temperatures in two clonal isolates of the model microcrustacean Daphnia pulex from more or less stressful environments, which showed a higher (clone M) or lower (clone G) tolerance to heat and starvation. RESULTS: The transcriptomic responses of clone G to acute heat stress (from 20 °C to 30 °C) and temperature acclimation (10 °C, 20 °C, and 24 °C) and the proteomic responses of both clones to acute heat, starvation, and heat-and-starvation stress comprised environment-specific and clone-specific elements. Acute stress (in particular heat stress) led to an early upregulation of stress genes and proteins (e.g., molecular chaperones) and a downregulation of metabolic genes and proteins (e.g., hydrolases). The transcriptomic responses to temperature acclimation differed clearly. They also varied depending on the temperature level. Acclimation to higher temperatures comprised an upregulation of metabolic genes and, in case of 24 °C acclimation, a downregulation of genes for translational processes and collagens. The proteomic responses of the clones M and G differed at any type of stress. Clone M showed markedly stronger and less stress-specific proteomic responses than clone G, which included the consistent expression of a specific heat shock protein (HSP60) and vitellogenin (VTG-SOD). CONCLUSIONS: The expression changes under acute stress can be interpreted as a switch from standard products of gene expression to stress-specific products. The expression changes under temperature acclimation probably served for an increase in energy intake (via digestion) and, if necessary, a decrease in energy expenditures (e.g, for translational processes). The stronger and less stress-specific proteomic responses of clone M indicate a lower degree of cell damage and an active preservation of the energy balance, which allowed adequate proteomic responses under stress, including the initiation of resting egg production (VTG-SOD expression) as an emergency reaction.

Reactive oxygen species (ROS) and the heat stress response of Daphnia pulex: ROS-mediated activation of hypoxia-inducible factor 1 (HIF-1) and heat shock factor 1 (HSF-1) and the clustered expression of stress genes.

BACKGROUND INFORMATION: Heat stress in ectotherms involves direct (e.g. protein damage) and/or indirect effects (temperature-induced hypoxia and ROS formation), which cause activation of the transcription factors (TF) heat shock factor 1 (HSF-1) and/or hypoxia-inducible factor 1 (HIF-1). The present study focused on the links between stress (ROS) signals, nuclear (n) and cytoplasmic (c) HSF-1/HIF-1 levels, and stress gene expression on mRNA and protein levels (e.g. heat-shock protein 90, HSP90) upon acute heat and ROS (H2 O2 ) stress. RESULTS: Acute heat stress (30°C) evoked fluctuations in ROS level. Different feeding regimens, which affected the glutathione (GSH) level, allowed altering the frequency of ROS fluctuations. Other data showed fluctuation frequency to depend also on ROS production rate. The heat-induced slow or fast ROS fluctuations (at high or low GSH levels) evoked slow or fast fluctuations in the levels of nHIF-1α, nHSF-1 and gene products (mRNAs and protein), albeit after different time delays. Time delays to ROS fluctuations were, for example,shorter for nHIF-1α than for nHSF-1 fluctuations, and nHIF-1α fluctuations preceded and nHSF-1 fluctuations followed fluctuations in HSP90 mRNA level. Cytoplasmic TF levels either changed little (cHIF-1α) or showed a steady increase (cHSF-1). Applying acute H2 O2 stress (at 20°C) revealed effects on nHIF-1α and mRNA levels, but no significant effects on nHSF-1 level. Transcriptome data additionally showed coordinated fluctuations of mRNA levels upon acute heat stress, involving mRNAs for HSPs and other stress proteins, with all corresponding genes carrying DNA binding motifs for HIF-1 and HSF-1. CONCLUSIONS: This study provided evidence for promoting effects of ROS and HIF-1 on early haemoglobin, HIF-1α and HSP90 mRNA expressions upon heat or ROS stress. The increasing cHSF-1 level likely affected nHSF-1 level and later HSP90 mRNA expression. SIGNIFICANCE: Heat stress evoked ROS fluctuations, with this stress signal forwarded via nHIF-1 and nHSF-1 fluctuations to stress gene expression. The frequency of ROS fluctuations seemed to integrate information about ROS productionrate and GSH antioxidant buffer capacity, resulting in stress protein expression of different speed. Results of this study suggest ROS as early (pre-damage) and protein defects as later (post-damage) stress signals to trigger heat stress responses.

Spontaneous Arm Movement Activity during Sleep in Epileptic and Non-Epileptic Patients.

PURPOSE: Epilepsy has a complex interaction with sleep. The purpose of this study was to explore the relation between spontaneous arm movements and sleep architecture in patients with epilepsy. METHODS: This prospective study included 53 patients with suspected epilepsy (44 ± 18 years; 30 females, 23 males) and 55 age-matched patients with non-epileptic seizures (42 ± 15: 27 females, 28 males). Twenty-four-hour-video-electroencephalography recordings were combined with accelerometry of movement activity of both arms using actiwatches. RESULTS: Patients with suspected epilepsy showed a higher occurrence of epileptic discharges (p = 0.0001) and abnormal focal slowing (p = 0.027) in the electroencephalogram (EEG) than the patients with non-epileptic seizures. Also, the epilepsy patients showed a shorter rapid eye movement-sleep duration compared to controls (0.0001). Accelerometry revealed that the patients with epilepsy moved their dominant right arm more frequently during the night (p = 0.014) than the controls, although there was no difference in arm movement activity during day time. CONCLUSION: The patients with reported epilepsy exhibited higher spontaneous arm movement activity during sleep. This may be related to abnormal sleep architecture or abnormal EEG activity but was not related to epileptic seizures.

Good clinical and radiographic outcome of cementless metal metaphyseal sleeves in total knee arthroplasty.

Background and purpose - The number of revision total knee arthroplasties (TKA) is continuously increasing, leading to a growing need for reliable management of metaphyseal bone loss. We evaluated patients operated with a TKA using metal metaphyseal sleeves for bone defects with a minimum 5-year follow-up. Patients and methods - 37 patients had been operated on. 3 patients died and 3 patients were lost during follow-up. Of the 31 remainders (20 women), 9 had been operated on with a primary TKA and 22 with a revision TKA at the index surgery. The mean age at surgery was 69 (54-89) years and the mean follow-up time was 7.4 (5-12) years. Bone defects were classified according to the Anderson Orthopaedic Research Institute classification (tibia: type I n = 9, type II n = 5 and type III n = 17; femur: type I n = 12, type II n = 3 and type III n = 16). Results - At final follow-up one-third experienced an improvement concerning walking aids and walking distance. Except for 1 patient, all had full extension and a mean knee flexion of 110 (90-140) degrees. VAS pain at rest was 13 (SD 25) and on movement 30 (SD 31). 7 patients were reoperated due to: infection (n = 4), periprosthetic fracture (n = 1), skin necrosis (n = 1), and wound rupture (n = 1). The cumulative 5-year survival rate for reoperation was 77% (CI 63-92) and for revision 97% (CI 91-100). At the time of final follow-up, the sleeves showed good osseointegration with no signs of progressive radiolucency or migration. Interpretation - Titanium sleeves are a promising option in managing difficult cases with metaphyseal bone defects in TKA, providing a stable construct with good medium-term radiographic outcome.

PMK-1 p38 MAPK promotes cadmium stress resistance, the expression of SKN-1/Nrf and DAF-16 target genes, and protein biosynthesis in Caenorhabditis elegans.

The mechanisms of cadmium (Cd) resistance are complex and not sufficiently understood. The present study, therefore, aimed at assessing the roles of important components of stress-signaling pathways and of ABC transporters under severe Cd stress in Caenorhabditis elegans. Survival assays on mutant and control animals revealed a significant promotion of Cd resistance by the PMK-1 p38 MAP kinase, the transcription factor DAF-16/FoxO, and the ABC transporter MRP-1. Transcriptome profiling by RNA-Seq on wild type and a pmk-1 mutant under control and Cd stress conditions revealed, inter alia, a PMK-1-dependent promotion of gene expression for the translational machinery. PMK-1 also promoted the expression of target genes of the transcription factors SKN-1/Nrf and DAF-16 in Cd-stressed animals, which included genes for molecular chaperones or immune proteins. Gene expression studies by qRT-PCR confirmed the positive effects of PMK-1 on DAF-16 activity under Cd stress and revealed negative effects of DAF-16 on the expression of genes for MRP-1 and DAF-15/raptor. Additional studies on pmk-1 RNAi-treated wild type and mutant strains provided further information on the effects of PMK-1 on SKN-1 and DAF-16, which resulted in a model of these relationships. The results of this study demonstrate a central role of PMK-1 for the processing of cellular responses to abiotic and biotic stressors, with the promoting effects of PMK-1 on Cd resistance mostly mediated by the transcription factors SKN-1 and DAF-16.

An fMRI study of training voluntary smooth circular eye movements.

Despite a large number of recent studies, the promise of fMRI methods to produce valuable insights into motor skill learning has been restricted to sequence learning paradigms, or manual training paradigms where a relatively advanced capacity for sensory-motor integration and effector coordination already exists. We therefore obtained fMRIs from 16 healthy adults trained in a new paradigm that demanded voluntary smooth circular eye movements without a moving target. This aimed to monitor neural activation during two possible motor learning processes: (a) the smooth pursuit control system develops a new perceptual-motor relationship and successfully becomes involved in voluntary action in which it is not normally involved or (b) the saccadic system normally used for voluntary eye movement and which only exhibits linear action skill develops new dynamic coordinative control capable of smooth circular movement. Participants were able to improve within half an hour, typically demonstrating saccadic movement with progressively reduced amplitudes, which better approximated smooth circular movement. Activity in the inferior premotor cortex was significantly modulated and decreased during the progress of learning. In contrast, activations in dorsal premotor and parietal cortex along the intraparietal sulcus, the supplementary eye field and the anterior cerebellum did not change during training. Thus, the decrease of activity in inferior premotor cortex was critically related to the learning progress in visuospatial eye movement control.

Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

Comparison of metal ion concentrations and implant survival after total hip arthroplasty with metal-on-metal versus metal-on-polyethylene articulations.

Background and purpose - Large metal-on-metal (MoM) articulations are associated with metal wear and corrosion, leading to increased metal ion concentrations and unacceptable revision rates. There are few comparative studies of 28-mm MoM articulations with conventional metal-on-polyethylene (MoP) couplings. We present a long-term follow-up of a randomized controlled trial comparing MoM versus MoP 28-mm articulations, focused on metal ions and implant survival. Patients and methods - 85 patients with a mean age of 65 years at surgery were randomized to a MoM (Metasul) or a MoP (Protasul) bearing. After 16 years, 38 patients had died and 4 had undergone revision surgery. 13 patients were unavailable for clinical follow-up, leaving 30 patients (n = 14 MoM and n = 16 MoP) for analysis of metal ion concentrations and clinical outcome. Results - 15-year implant survival was similar in both groups (MoM 96% [95% CI 88-100] versus MoP 97% [95% CI 91-100]). The mean serum cobalt concentration was 4-fold higher in the MoM (1.5 µg/L) compared with the MoP cohort (0.4 µg/L, p < 0.001) and the mean chromium concentration was double in the MoM (2.2 µg/L) compared with the MoP cohort (1.0 µg/L, p = 0.05). Mean creatinine levels were similar in both groups (MoM 93 µmol/L versus MoP 92 µmol/L). Harris hip scores differed only marginally between the MoM and MoP cohorts. Interpretation - This is the longest follow-up of a randomized trial on 28-mm MoM articulations, and although implant survival in the 2 groups was similar, metal ion concentrations remained elevated in the MoM cohort even in the long term.

Between- and within-site variability of fMRI localizations.

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.

Hypoxia-inducible haemoglobins of Daphnia pulex and their role in the response to acute and chronic temperature increase.

Daphnia pulex is challenged by severe oxygen and temperature changes in its habitat. In response to hypoxia, the equipment of oxygen transport proteins is adjusted in quantity and quality by differential expression of haemoglobin isoforms. This study focuses on the response of 20°C acclimated animals to elevated temperature using transcriptomic and proteomic approaches. Acute temperature stress (30°C) induced the hypoxia-inducible Hb isoforms most strongly, resulting in an increase of the haemoglobin mRNA pool by 70% within 8h. Long-term-acclimation to moderately elevated temperature (24°C) only evoked minor changes of the Hb mRNA suite. Nevertheless, the concentration of the hemolymph pool of haemoglobin was elevated by 80%. In this case, the constitutive Hb isoforms showed the strongest increase, with Hb01 and Hb02 contributing by 64% to the total amount of respiratory protein. The regulation patterns upon acute temperature stress likely reflect temperature-induced tissue hypoxia, whereas in case of persisting exposure to moderately elevated temperature, acclimation processes enabled the successful return to oxygen homeostasis. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins.

The JNK-like MAPK KGB-1 of Caenorhabditis elegans promotes reproduction, lifespan, and gene expressions for protein biosynthesis and germline homeostasis but interferes with hyperosmotic stress tolerance.

AIMS: This study focused on the role of the JNK-like MAPK (mitogen-activated protein kinase) KGB-1 (kinase, GLH-binding 1) for osmoprotection and other vital functions. METHODS: We mapped KGB-1 expression patterns and determined lifespan, reproduction and survival rates as well as changes in body volume, motility, and GPDH (glycerol-3-phosphate dehydrogenase) activity for glycerol production in wildtype (WT), different signaling mutants (including a kgb-1 deletion mutant, kgb-1∆) and RNAi-treated worms under control and hyperosmotic conditions. KGB-1-mediated gene expressions were studied, for instance, by RNA Sequencing, with the resulting transcriptome data analyzed using orthology-based approaches. RESULTS: Surprisingly, mutation/RNAi of kgb-1 and fos-1 (gene for an AP-1, activator protein 1, element) significantly promoted hyperosmotic resistance, even though hyperosmotic GPDH activity was higher in WT than in kgb-1∆. KGB-1 and moderate hyperosmolarity promoted and severe hyperosmolarity repressed kgb-1, fos-1, and jun-1 (gene for another AP-1 element) expression. Transcriptome profiling revealed, for instance, down-regulated genes for protein biosynthesis and up-regulated genes for membrane transporters in kgb-1∆ and up-regulated genes for GPDH-1 or detoxification in WT, with the latter indicating cellular damage and less effective osmoprotection in WT. CONCLUSION: KGB-1 promotes reproduction and lifespan and fosters gene expressions for AP-1 elements, protein biosynthesis, and balanced gametogenesis, but inhibits expressions for membrane transporters perhaps in order to control energy consumption. Reduced protein biosyntheses and enhanced membrane transports in kgb-1∆ most likely contribute to the high hyperosmotic tolerance of the mutant by easing the burden of the existing chaperone machinery and promoting regulatory volume increases upon hyperosmotic stress.