Learning-related congruent and incongruent changes of excitation and inhibition in distinct cortical areas.

Excitatory and inhibitory neurons in diverse cortical regions are likely to contribute differentially to the transformation of sensory information into goal-directed motor plans. Here, we investigate the relative changes across mouse sensorimotor cortex in the activity of putative excitatory and inhibitory neurons-categorized as regular spiking (RS) or fast spiking (FS) according to their action potential (AP) waveform-comparing before and after learning of a whisker detection task with delayed licking as perceptual report. Surprisingly, we found that the whisker-evoked activity of RS versus FS neurons changed in opposite directions after learning in primary and secondary whisker motor cortices, while it changed similarly in primary and secondary orofacial motor cortices. Our results suggest that changes in the balance of excitation and inhibition in local circuits concurrent with changes in the long-range synaptic inputs in distinct cortical regions might contribute to performance of delayed sensory-to-motor transformation.

Direct visualization of pre-protamine 2 detects protamine assembly failures and predicts ICSI success.

Histone-to-protamine transition is an essential step in the generation of fully functional spermatozoa in various mammalian species. In human and mouse, one of the two protamine-encoding genes produces a precursor pre-protamine 2 (pre-PRM2) protein, which is then processed and assembled. Here, we design an original approach based on the generation of pre-PRM2-specific antibodies to visualize the unprocessed pre-PRM2 by microscopy, flow cytometry and immunoblotting. Using mouse models with characterized failures in histone-to-protamine replacement, we show that pre-PRM2 retention is tightly linked to impaired nucleosome disassembly. Additionally, in elongating/condensing spermatids, we observe that pre-PRM2 and transition protein are co-expressed spatiotemporally, and their physical interaction suggests that these proteins act simultaneously rather than successively during histone replacement. By using our anti-human pre-PRM2 antibody, we also measured pre-PRM2 retention rates in the spermatozoa from 49 men of a series of infertile couples undergoing ICSI, which shed new light on the debated relation between pre-PRM2 retention and sperm parameters. Finally, by monitoring 2-pronuclei embryo formation following ICSI, we evaluated the fertilization ability of the sperm in these 49 patients. Our results suggest that the extent of pre-PRM2 retention in sperm, rather than pre-PRM2 accumulation per se, is associated with fertilization failure. Hence, anti-pre-PRM2 antibodies are valuable tools that could be used in routine monitoring of sperm parameters in fertility clinics, as well as in experimental research programmes to better understand the obscure process of histone-to-protamine transition.

Relationship between obesity-related markers, biochemical metabolic parameters, hormonal profiles and sperm parameters among men attending an infertility clinic.

Obesity causes many health problems as well as has negative effects on fertility. However, little is known about the association between obesity-related markers (hip circumference (HC), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), body fat mass (BFM), skeletal muscle (SM), resting metabolism (RM), visceral fat (VF), and visceral adiposity index (VAI)) and sperm parameters. This cross-sectional study was conducted on 98 men in three groups: normal-weight (Nw; body mass index: BMI < 25 kg/m2 ), overweight (Ow; BMI: 25-29 kg/m2 ), and obese (Ob; BMI: 30-35 kg/m2 ) to investigate this issue. The mean WC, HC, WHtR, BFM, SM, RM, and VF were remarkably higher (p < 0.001) for subjects in the Ob group than in Ow and Nw. In Nw, positive correlations were observed between BFM (r = 0.402) and VAI (r = 0.353) and sperm progressive motility (p < 0.05). In Ob males, there was a positive correlation (r = 0.430) between sperm progressive motility and height and a negative relation (r = -0.447) between sperm progressive motility and WHtR. We found the association between serum testosterone (T) levels, T/estradiol ratios, and semen parameters being dependent on obesity-related markers which confirms the negative effects of obesity on male hormones. In conclusion, WHtR is a valuable parameter in infertility clinics that warrants further studies.

The alteration of PLCζ protein expression in unexplained infertile and asthenoteratozoospermic patients: A potential effect on sperm fertilization ability.

Failed oocyte activation has been observed in unexplained infertile (UI) and asthenoteratozoospermic (AT) men. The deficiency of phospholipase C-zeta (PLCζ) could be a possible reason for such failures and has not been studied yet. We investigated the expression and localization of PLCζ protein in the sperms of patients with UI and AT conditions. The relationships between PLCζ-related parameters with male age, sperm characteristics, DNA integrity, and cellular maturity were assessed. Semen samples were collected from fertile (n = 40), UI (n = 40), and AT (n = 40) men. Subsequently, semen analysis, DNA fragmentation, hyaluronic acid-binding ability, and PLCζ level along with its distribution were evaluated using computer-assisted sperm analyzer, sperm chromatin structure assay (SCSA), hyaluronic acid-binding assay (HBA), western blot analysis and immunofluorescence microscopy, respectively. Unlike SCSA, the values of HBA, and PLCζ expression were significantly reduced in UI and AT patients compared to fertile men, whereas no significant differences were observed among the experimental groups in terms of PLCζ localization patterns. The regression analysis also showed that HBA is the only variable associated with PLCζ levels. Furthermore, the correlation of male age with PLCζ localization in postacrosomal, equatorial, and acrosomal+postacrosomal+equatorial (A+PA+E) patterns, as well as the relation of normal morphology, with the (A+PA+E) pattern, remained in the regression model. Our findings indicated that reduced PLCζ level along with the increased DNA fragmentation and impaired maturation may be possible etiologies of decreased fertilization in the studied subjects.

Knockout serum replacement is an efficient serum substitute for cryopreservation of human spermatozoa.

The freeze-thaw procedure causes irreversible structural and functional changes in human spermatozoa. In order to decrease the detrimental effects of cryopreservation and improve the quality of post-thawed spermatozoa, the constituents of the freezing solution attracted considerable attention. In this study, for the first time, we evaluated the efficacy of knockout serum replacement (KSR) as a substitute for human serum albumin (HSA) for cryopreservation of human spermatozoa. Twenty semen samples were collected from normozoospermic men and divided them into five equal groups. One of the aliquots was diluted with glycerol-based medium as a control group (CON). The other four aliquots were diluted with the sucrose solution containing 5% HSA (H5), 10% HSA (H10), 5% KSR (K5), and 10% KSR (K10). The diluted samples were frozen and preserved in liquid nitrogen. Post thawed sperm parameters including motion characteristics, viability, membrane integrity, mitochondrial activity, acrosome integrity and DNA intactness in all of the sucrose-based groups were comparable with glycerol-based medium. The replacement of HSA by 10% KSR in the freezing medium resulted in significantly higher post-thawed viability, acrosome integrity and DNA intactness compared with other sucrose-based groups. In conclusion, the addition of 10% KSR to the sucrose-based freezing solution improves the quality of post-thawed human spermatozoa and may have potential to develop chemically defined freezing medium.

Inclusion of ovine enriched serum with vitamin E and polyunsaturated fatty acids in the freezing medium: a new strategy to improve human frozen-thawed sperm parameters.

The objective was to evaluate the effect of inclusion of 2.5% and 5% ovine serum, enriched with vitamin E (Vit E) and fish oil (FO), in human sperm freezing medium. Serum samples were prepared from sixteen rams (n = 4) feeding on a without supplemented diet, and diets supplemented with Vit E, FO and Vit E + FO. Semen samples, from 60 normozoospermic men, were frozen in: (I) a commercial freezing medium (SpermFreeze™; control medium), (II) the commercial freezing medium containing foetal bovine serum, (III) the commercial freezing medium + nonenriched serum (serum group), (IV) the commercial freezing medium + Vit E enriched serum (Vit E group), (V) the commercial freezing medium + FO enriched serum (FO group) and (VI) the commercial freezing medium + Vit E + FO enriched serum (Vit E + FO group). Sperm total and progressive motility, morphology, viability and plasma membrane integrity were significantly higher (p ≤ .05) in Vit E and Vit E + FO groups compared with the control group. Mitochondrial membrane potential did not differ between treatments (p > .05). It was concluded that ovine serum enriched with vitamin E and vitamin E + FO improved the quality of human spermatozoa but enriched serum containing FO could not improve the sperm cryo-injuries.

Intense and unpredictable perturbations during gait training improve dynamic balance abilities in chronic hemiparetic individuals: a randomized controlled pilot trial.

BACKGROUND: Previous studies have assessed the effects of perturbation training on balance after stroke. However, the perturbations were either applied while standing or were small in amplitude during gait, which is not representative of the most common fall conditions. The perturbations were also combined with other challenges such as progressive increases in treadmill speed. OBJECTIVE: To determine the benefit of treadmill training with intense and unpredictable perturbations compared to treadmill walking-only training for dynamic balance and gait post-stroke. METHODS: Twenty-one individuals post-stroke with reduced dynamic balance abilities, with or without a history of fall and ability to walk on a treadmill without external support or a walking aid for at least 1 min were allocated to either an unpredictable gait perturbation (Perturb) group or a walking-only (NonPerturb) group through covariate adaptive randomization. Nine training sessions were conducted over 3 weeks. NonPerturb participants only walked on the treadmill but were offered perturbation training after the control intervention. Pre- and post-training evaluations included balance and gait abilities, maximal knee strength, balance confidence and community integration. Six-week phone follow-ups were conducted for balance confidence and community integration. Satisfaction with perturbation training was also assessed. RESULTS: With no baseline differences between groups (p > 0.075), perturbation training yielded large improvements in most variables in the Perturb (p < 0.05, Effect Size: ES > .46) group (n = 10) and the NonPerturb (p ≤ .089, ES > .45) group (n = 7 post-crossing), except for maximal strength (p > .23) in the NonPerturb group. Walking-only training in the NonPerturb group (n = 8, pre-crossing) mostly had no effect (p > .292, ES < .26), except on balance confidence (p = .063, ES = .46). The effects of the gait training were still present on balance confidence and community integration at follow-up. Satisfaction with the training program was high. CONCLUSION: Intense and unpredictable gait perturbations have the potential to be an efficient component of training to improve balance abilities and community integration in individuals with chronic stroke. Retrospective registration: ClinicalTrials.gov. March 18th, 2020. Identifier: NCT04314830.

Dietary trans and saturated fatty acids effects on semen quality, hormonal levels and expression of genes related to steroid metabolism in mouse adipose tissue.

Our objectives were to assess sperm alteration and adipose tissue (AT) genes expression related to steroid metabolism subsequent to fatty acids consumption. Twenty-nine mature male mice were divided into: fat diet (FD; n = 15) and the control group (n = 14). FD group was fed with low level of trans and saturated fatty acids source for 60 days. Sperm parameters, levels of hormones and the mRNA abundance of the target genes in AT were assessed. The sperm concentration, total and progressive motilities were lower in FD group compared to that of control (p < 0.01). Blood estradiol levels increased in FD (p < 0.001), whereas no significant difference was observed in testosterone. The mRNA levels of StAR, CYP11A1, CYP17A1, 17ßHSD7 and 17ßHSD12 in AT of FD were higher than those of the control (p < 0.05). In contrast, mRNA level of Cyp19a1 in FD was significantly (p < 0.05) lower than that of control. 17ßHSD12 and 17ßHSD7 (as oestrogenic genes) increased, while 17ßHSD5 and 17ßHSD3 (as androgenic genes) remained unchanged, indicating that dietary trans/saturated fatty acids affect AT genes expression. Probably, sperm parameters were altered by increment of expression level of genes involved in oestrogenic metabolism rather than those engaged in androgenic metabolism after fatty acids consumption.

Proteomic analysis and microtubule dynamicity of human sperm in electromagnetic cryopreservation.

The proteomic changes, microtubule dynamicity, and quality parameters of human sperm were investigated during cryopreservation in an extremely low electromagnetic field (ELEF) condition. Semen samples were obtained from 210 healthy individuals with normospermia and then were divided into three experimental groups: fresh control, frozen control, and frozen ELEF group. Shotgun proteomics was performed to assess the identification of microtubule proteins of the sperm in experimental groups. Microtubule dynamicity, secondary, and tertiary structure modifications of tubulins, characteristics of transmission electron microscopy of sperm as well as sperm quality parameters were evaluated. The expression ratios of α- and ß-tubulins were significantly increased after cryopreservation compared with fresh control while this ratio was not significantly different in frozen ELEF group. The expression ratio of tubulin polymerization-promoting protein was significantly decreased after cryopreservation compared with fresh control. The length, width, and the activity of microtubule, secondary, and tertiary structures of tubulins, motility, and the viability of the sperm were decreased in frozen control as compared with fresh control. The microtubule activity, secondary, and tertiary structures of sperm tubulin in frozen ELEF group were higher than frozen control. Transmission electron microscopy of microtubules showed that the size of the width and length of the microtubules in frozen ELEF group were greater than frozen control. Motility, viability, and reactive oxygen species levels were improved in frozen ELEF group when compared with frozen control. While the microtubule dynamicity of the sperm was affected by the cryopreservation, this trait was improved during the electromagnetic cryopreservation resulted in better motility and viability.

Sperm cryopreservation: A review on current molecular cryobiology and advanced approaches.

The cryopreservation of spermatozoa was introduced in the 1960s as a route to fertility preservation. Despite the extensive progress that has been made in this field, the biological and biochemical mechanisms involved in cryopreservation have not been thoroughly elucidated to date. Various factors during the freezing process, including sudden temperature changes, ice formation and osmotic stress, have been proposed as reasons for poor sperm quality post-thaw. Little is known regarding the new aspects of sperm cryobiology, such as epigenetic and proteomic modulation of sperm and trans-generational effects of sperm freezing. This article reviews recent reports on molecular and cellular modifications of spermatozoa during cryopreservation in order to collate the existing understanding in this field. The aim is to discuss current freezing techniques and novel strategies that have been developed for sperm protection against cryo-damage, as well as evaluating the probable effects of sperm freezing on offspring health.

Tactile perception and working memory in rats and humans.

Primates can store sensory stimulus parameters in working memory for subsequent manipulation, but until now, there has been no demonstration of this capacity in rodents. Here we report tactile working memory in rats. Each stimulus is a vibration, generated as a series of velocity values sampled from a normal distribution. To perform the task, the rat positions its whiskers to receive two such stimuli, "base" and "comparison," separated by a variable delay. It then judges which stimulus had greater velocity SD. In analogous experiments, humans compare two vibratory stimuli on the fingertip. We demonstrate that the ability of rats to hold base stimulus information (for up to 8 s) and their acuity in assessing stimulus differences overlap the performance demonstrated by humans. This experiment highlights the ability of rats to perceive the statistical structure of vibrations and reveals their previously unknown capacity to store sensory information in working memory.

The effects of MitoQ as a mitochondrial-targeted antioxidant in a plant-based extender on buck sperm quality parameters during cryopreservation.

Sperm cryopreservation plays an important role in the artificial insemination (AI) industry of small ruminants. It, however the use of frozen-thawed goat semen is limited due to the insufficient number of sperm with good biological functions. Mitochondria are the most sensitive organelles to cryopreservation damage in sperm. This study was conducted to determine the effects of MitoQ, the mitochondrial-targeted antioxidant, in a plant-based extender on the quality parameters of Markhoz goat sperm after the freezing and thawing process. Semen samples were collected and diluted in the extender, divided into five equal aliquots and supplemented with 0, 1, 10, 100 and 1000 nM MitoQ and cryopreserved in liquid nitrogen. After thawing, sperm motility, membrane functionality, abnormal morphology, mitochondrial activity, acrosome integrity, lipid peroxidation (LPO), DNA fragmentation, reactive oxygen species (ROS) concentration, viability and apoptotic-like changes were measured. The use of 10 and 100 nM MitoQ resulted in higher (P≤0.05) total motility (TM), progressive motility (PM), viability, membrane functionality, mitochondrial activity, and acrosome integrity compared to the other groups. On the other hand, LPO, apoptotic-like changes, DNA fragmentation and ROS concentration were lower (P≤0.05) in MQ10 and MQ100 groups compared to the other groups. MitoQ has no effect (P>0.05) on sperm abnormal morphology and velocity parameters. In conclusion, MitoQ can reduce oxidative stress by regulating mitochondrial function during the cryopreservation process of buck sperm and could be an effective additive in the cryopreservation media to protect sperm quality.

Distributed and specific encoding of sensory, motor, and decision information in the mouse neocortex during goal-directed behavior.

Goal-directed behaviors involve coordinated activity in many cortical areas, but whether the encoding of task variables is distributed across areas or is more specifically represented in distinct areas remains unclear. Here, we compared representations of sensory, motor, and decision information in the whisker primary somatosensory cortex, medial prefrontal cortex, and tongue-jaw primary motor cortex in mice trained to lick in response to a whisker stimulus with mice that were not taught this association. Irrespective of learning, properties of the sensory stimulus were best encoded in the sensory cortex, whereas fine movement kinematics were best represented in the motor cortex. However, movement initiation and the decision to lick in response to the whisker stimulus were represented in all three areas, with decision neurons in the medial prefrontal cortex being more selective, showing minimal sensory responses in miss trials and motor responses during spontaneous licks. Our results reconcile previous studies indicating highly specific vs. highly distributed sensorimotor processing.

Cell-type specific synaptic plasticity in dorsal striatum is associated with punishment-resistance compulsive-like cocaine self-administration in mice.

Addiction-related compulsion-like behavior can be modeled in rodents with drug self-administration (SA) despite harmful consequences. Recent studies suggest that the potentiation of glutamatergic transmission at the orbitofrontal cortex (OFC) to dorsal striatum (DS) synapses drives the transition from controlled to compulsion-like SA. However, the timing of the induction of this synaptic plasticity remains elusive. Here, mice were first allowed to intravenously self-administer cocaine. When mice had to endure a risk of electrical foot shock, only a fraction persevered in cocaine SA. In these persevering mice, we recorded high A/N ratios (AMPA-R/NMDA-R: α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor) in both types of spiny projection neurons (i.e., D1 and D2 dopamine receptor-expressing SPNs). By contrast, when we prepared slices at the end of the acquisition period, in all mice, the A/N was high in D1R- but not D2R-SPNs. These results indicate that the transition to compulsion-like cocaine SA emerges during the punishment sessions, where synapses onto D2R-SPNs are strengthened. In renouncing individuals, the cocaine-evoked strengthening in D1R-SPNs is lost. Our study thus reveals the cell-type specific sequence of the induction of plasticity that eventually may cause compulsion-like SA.

Sublethal Xanthine Oxidase Stress Prefreezing of Bull Sperm Improves the Post-Thaw Functionality and Fertility Potential Parameters.

Oxidative stress during cryopreservation causes mechanical, biochemical, and structural damage to the sperm, leading to lower viability and fertility potential. In recent years, a novel method based on the use of mild stress for preconditioning of sperm before cryopreservation has been applied to improve the quality of thawed sperm, although its molecular mechanism remains unknown. In this study, we investigated the protective effects of sublethal oxidative stress by xanthine oxidase (XO) on thawed bull sperm performance through modulations of mitochondrial uncoupling protein 2 (UCP2) expression. Semen samples were collected from six bulls, then mixed and divided into four aliquots: frozen control (XO-0) and frozen groups treated with different concentrations of XO, 0.01 µM (XO-0.01), 0.1 µM (XO-0.1), and 1 µM (XO-1). Thawed sperm were evaluated for motion parameters, viability, acrosome integrity, mitochondria activity, membrane integrity, and UCP2 expression. A significant increase of total motility and viability rate was observed in XO-0.1 compared with other frozen groups (p < 0.05). The highest percentage of progressive motility was in XO-0.01 and XO-0.1 compared with other groups (p < 0.05). Moreover, a significantly higher level of sperm mitochondrial membrane potential and membrane integrity was observed in XO-0.1 (p < 0.05). We also found the lowest percentage of sperm mitochondria activity in XO-1 (p < 0.05). In addition, the highest expression of UCP2 was observed in XO-1 (p < 0.05). Our findings suggest that stress preconditioning of bull sperm before cryopreservation can improve thawed sperm functions, which might be mediated through an increase of UCP2 expression.

Beneficial effects of trehalose and gentiobiose on human sperm cryopreservation.

The protection of human sperm during cryopreservation is of great importance to infertility. Recent studies have shown that this area is still a long way from its ultimate aim of maintaining the maximum viability of sperm in cryopreservation. The present study used trehalose and gentiobiose to prepare the human sperm freezing medium during the freezing-thawing. The freezing medium of sperm was prepared with these sugars, and the sperm were then cryopreserved. The viable cells, sperm motility parameters, sperm morphology, membrane integrity, apoptosis, acrosome integrity, DNA fragmentation, mitochondrial membrane potential, reactive oxygen radicals, and malondialdehyde concentration was evaluated using standard protocols. A higher percentage of the total and progressive motility, rate of viable sperm, cell membrane integrity, DNA and acrosome integrity, and mitochondrial membrane potential were observed in the two frozen treatment groups compared to the frozen control. The cells had less abnormal morphology due to treatment with the new freezing medium than the frozen control. The higher malondialdehyde and DNA fragmentation were significantly observed in the two frozen treatment groups than in the frozen control. According to the results of this study, the use of trehalose and gentiobiose in the sperm freezing medium is a suitable strategy for sperm freezing to improve its motion and cellular parameters.

Alpha-Lipoic Acid Supplementation for Male Partner of Couples with Recurrent Pregnancy Loss: A Post hoc analysis in Clinical Trial.

BACKGROUND: Increased sperm DNA damage is known as one of the causes of recurrent pregnancy loss (RPL) which can be due to increased levels of oxidative stress. Therefore, the aim of this study was to assess the effect of alpha-lipoic acid (ALA) on sperm parameters and sperm functions in couples with a history of RPL. MATERIALS AND METHODS: In this post hoc analysis in clinical trial study, a total of 37 couples with RPL (n=12 and n=25 for placebo and ALA groups, respectively) were considered. Men were treated with ALA (600 mg/day) or placebo for 80 days. Semen samples were acquired from the participants before initiation and after completion of the medication course and assessed regarding conventional sperm parameters, chromatin damage/integrity, intracellular oxidative stress, lipid peroxidation, and seminal antioxidant characteristics. Individuals were further followed up for twelve months for pregnancy occurrence and outcomes. Finally, after excluding patients with no history of RPL, the data was analyzed. RESULTS: No significant differences were observed between the baseline measures of the aforementioned parameters except for seminal volume. After the intervention, the mean sperm DNA damage, protamine deficiency, and persisted histones were significantly lower in the ALA group than in placebo receivers (P<0.05). A decrease in the mean of seminal total antioxidant capacity (P=0.03), malondialdehyde (P=0.02), and sperm DNA damage (P=0.004) as well as an increase in sperm total motility (P=0.04) after treatment with ALA was noticed. In addition, the mean of protamine deficiency and persisted histones were declined post-ALA therapy (P=0.003 and 0.002, respectively). The percentage of spontaneous pregnancy in the ALA group (4 of 25 cases; 16%) was higher than in the placebo group (1 of 12, 8.3%). CONCLUSION: ALA-therapy attenuates sperm DNA damage and lipid peroxidation while enhancing sperm total motility and chromatin compaction in the male partner of couples with PRL (registration number: IRCT20190406043177N1).

Alpha-Lipoic Acid Ameliorates Sperm DNA Damage and Chromatin Integrity in Men with High DNA Damage: A Triple Blind Randomized Clinical Trial.

OBJECTIVE: Evidence suggests the contributory role of oxidative stress (OS) to sperm DNA damage and eventually, male infertility. Antioxidant supplementation has exhibited favorable results regarding seminal OS, sperm DNA damage, and chromatin integrity. We aimed to evaluate the effect of alpha-lipoic acid (ALA) supplementation on semen analysis, sperm DNA damage, chromatin integrity, and seminal/intracellular OS in infertile men with high sperm DNA damage. MATERIALS AND METHODS: In this randomized triple-blind placebo-controlled clinical trial study, we opted for a triple-blind controlled clinical trial design. Considering the study's inclusion criteria for the level of sperm DNA fragmentation (higher than the threshold of 30 and 15%), 70% of participants were selected for this clinical research study. Subjects were divided into case and control groups receiving oral ALA (600 mg/day) and placebo for eighty days, respectively. Sperm parameters and functional tests were examined and compared before and after treatment. The final sample size was 34 and 29 for ALA and placebo receivers, respectively. RESULTS: No significant differences were observed about anthropometrics and baseline measures of semen analysis, DNA damage, OS, and chromatin integrity between the two groups. Conventional semen parameters were enhanced insignificantly in both groups (P>0.05). DNA damage decreased significantly in the ALA group, as per sperm chromatin structure assay (SCSA, P<0.001). Moreover, chromomycin A3 (CMA3) staining results indicated a decrease in nuclear protamine deficiency post-ALA therapy (P=0.004). Lipid peroxidation decreased significantly after treatment with ALA (P=0.003). Further, seminal antioxidant capacity/activity did not differ significantly in either of the groups (registration number: IRCT20190406043177N1). CONCLUSION: An 80-day course of oral ALA supplementation (600 mg/day) alleviates sperm OS, DNA damage, and chromatin integrity in men with high sperm DNA damage.

Rapid suppression and sustained activation of distinct cortical regions for a delayed sensory-triggered motor response.

The neuronal mechanisms generating a delayed motor response initiated by a sensory cue remain elusive. Here, we tracked the precise sequence of cortical activity in mice transforming a brief whisker stimulus into delayed licking using wide-field calcium imaging, multiregion high-density electrophysiology, and time-resolved optogenetic manipulation. Rapid activity evoked by whisker deflection acquired two prominent features for task performance: (1) an enhanced excitation of secondary whisker motor cortex, suggesting its important role connecting whisker sensory processing to lick motor planning; and (2) a transient reduction of activity in orofacial sensorimotor cortex, which contributed to suppressing premature licking. Subsequent widespread cortical activity during the delay period largely correlated with anticipatory movements, but when these were accounted for, a focal sustained activity remained in frontal cortex, which was causally essential for licking in the response period. Our results demonstrate key cortical nodes for motor plan generation and timely execution in delayed goal-directed licking.

Model system for measuring the effects of position and curvature of fiber reinforcement within a dental composite.

PURPOSE: The aim of this study was to compare the effect of fiber curvature and position on flexural strength (FS), toughness, and elastic modulus in a dental flowable composite test specimen. METHODS AND MATERIALS: Test specimens made of composite resin (Denfil Flow) were reinforced with preimpregnated glass fibers (Interlig). Control specimens (group A) did not contain fiber reinforcement. Fibers were placed with different positions and orientations into the test specimens (2 mm x 2 mm x 25 mm) (groups B, C, D). The test specimens (n = 10) were stored in distilled water for 3 days at 37 degrees C before testing in a three-point loading test (ISO 10477) at a crosshead speed of 1 mm/min to determine FS, flexural modulus (FM), and toughness. Data were analyzed with 1-way analysis of variance and Tukey HSD (sigma= 0.05). RESULTS: The FM varied from 4.7 +/- 0.5 to 6.7 +/- 0.5 GPa. The lowest flexural strength and toughness values in reinforced specimens resulted from compression side fiber reinforcement (132 +/- 12 MPa, 21 +/- 4 MJ) and the highest from curved fiber reinforcement (174 +/- 8 MPa, 83 +/- 28 MJ), though this was not statistically significant from tension-side reinforcement. Although the toughness of the curved reinforced group was significantly higher than other groups, the flexural strength of curved reinforcement was not significantly higher than tension-side reinforcement. CONCLUSION: Position and fiber orientation influenced the flexural strength, FM, and toughness. The most effective in increasing toughness was curved placement of fibers.