Miracle-dz/UniFAR-FTUs huggingface dataset:
A yeast recombination assay to characterize human BRCA1 missense variants of unknown pathological significance

The BRCA1 tumor suppressor gene is found mutated in familial breast cancer. Although many of the mutations are clearly pathological because they give rise to truncated proteins, several missense variants of uncertain pathological consequences have been identified. A novel functional assay to screen for BRCA1 missense variants in a simple genetic system could be very useful for the identification of potentially deleterious mutations. By using two prediction computer programs, Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping (PolyPhen), seven nonsynonymous missense BRCA1 variants likely disrupting the gene function were selected as potentially deleterious. The budding yeast Saccharomyces cerevisiae (S. cerevisiae) was used to test these cancer‐related missense mutations for their ability to affect cell growth and homologous recombination (HR) at the HIS3 and ADE2 loci. The variants localized in the BRCA1 C‐Terminus (BRCT) domain did not show any growth inhibition when overexpressed in agreement with previous results. Overexpression of either wild‐type BRCA1 or two neutral missense variants did not increase yeast HR but when cancer‐related variants were overexpressed a significant increase in recombination was observed. Results clearly showed that this genetic system can be useful to discriminate between neutral and deleterious BRCA1 missense variants. Hum Mutat 0, 1–11, 2008. © 2008 Wiley‐Liss, Inc.
In silico analysis of missense substitutions using sequence‐alignment based methods

Genetic testing for mutations in high‐risk cancer susceptibility genes often reveals missense substitutions that are not easily classified as pathogenic or neutral. Among the methods that can help in their classification are computational analyses. Predictions of pathogenic vs. neutral, or the probability that a variant is pathogenic, can be made based on: 1) inferences from evolutionary conservation using protein multiple sequence alignments (PMSAs) of the gene of interest for almost any missense sequence variant; and 2) for many variants, structural features of wild‐type and variant proteins. These in silico methods have improved considerably in recent years. In this work, we review and/or make suggestions with respect to: 1) the rationale for using in silico methods to help predict the consequences of missense variants; 2) important aspects of creating PMSAs that are informative for classification; 3) specific features of algorithms that have been used for classification of clinically‐observed variants; 4) validation studies demonstrating that computational analyses can have predictive values (PVs) of ∼75 to 95%; 5) current limitations of data sets and algorithms that need to be addressed to improve the computational classifiers; and 6) how in silico algorithms can be a part of the “integrated analysis” of multiple lines of evidence to help classify variants. We conclude that carefully validated computational algorithms, in the context of other evidence, can be an important tool for classification of missense variants. Hum Mutat 29(11), 1327–1336, 2008. © 2008 Wiley‐Liss, Inc.
Association between traditional standing vertical jumps and a soccer-specific vertical jump

Abstract The present study aimed to determine the relationships between a soccer-specific vertical jump (ssVJ) test, that included common elements of a soccer VJ (e.g. run-up and intention to head), and three traditional VJ tests using elite soccer players. A secondary purpose of this study was to determine the reliability of the VJs used in the analysis. A randomised order and counterbalanced design was used to assess the relationships between these VJs [countermovement jump (CMJ), drop jump for height (DJh), drop jump for maximum height and minimum ground contact time (DJh/t) and the ssVJ]. Take-off velocity, contact time and flight time were the dependent variables of interest and compared between jumps. Intra-class correlation coefficient (ICC) and coefficient of variation (CV) were used as measures of inter-session reliability. All VJ tests were found to have high ICCs (0.89–0.99) and acceptable within-subject CVs (<7.5%). All the ssVJ dependent variables were not significantly related (r<0.44) with similar variables from the CMJ and DJh tests and only moderately related (r=~0.49) with the DJh/t test variables. In addition, the DJh/t variables were not significantly correlated (r<0.47) with DJh and CMJ test variables. In conclusion, it would seem that the proposed ssVJ test and CMJ or DJh tests assess different leg qualities and thought should be given before using them interchangeably to assess or develop the same performance measures (i.e. velocity at take-off or jump height).
Prediction and assessment of splicing alterations: implications for clinical testing

Sequence variants that may result in splicing alterations are a particular class of inherited variants for which consequences can be more readily assessed, using a combination of bioinformatic prediction methods and in vitro assays. There is also a general agreement that a variant would invariably be considered pathogenic on the basis of convincing evidence that it results in transcript(s) carrying a premature stop codon or an in‐frame deletion disrupting known functional domain(s). This commentary discusses current practices used to assess the clinical significance of this class of variants, provides suggestions to improve assessment, and highlights the issues involved in routine assessment of potential splicing aberrations. We conclude that classification of sequence variants that may alter splicing is greatly enhanced by supporting in vitro analysis. Additional studies that assess large numbers of variants for induction of splicing aberrations and exon skipping are needed to define the contribution of splicing/exon skipping to cancer and disease. These studies will also provide the impetus for development of algorithms that better predict splicing patterns. To facilitate variant classification and development of more specific bioinformatic tools, we call for the deposition of all laboratory data from splicing analyses into national and international databases. Hum Mutat 29(11), 1304–1313, 2008. © 2008 Wiley‐Liss, Inc.
Upper body force production after a low-volume static and dynamic stretching

Abstract This study investigated the acute effect of a low-volume static and dynamic stretching on maximal isometric peak force (MIPF), time to maximal isometric force (TMIF), rate of force production (RFP) and average amplitude of the surface EMG (AvgEMG) of the main agonist muscles acting on the bench press maximum isometric force exercise. Thirty subjects were randomly divided into three groups: static stretch (SG: 22.8±5.6 years, 176.6±3.5 cm, 74.4±5.9 kg), dynamic stretch (DG: 21.4±3.9 years, 178.4±7.2 cm, 71.7±8.2 kg) and control group (CG: 20.4±3.6 years, 179.8±5.8 cm, 74.4±9.8 kg). SG performed two 30-s repetitions and DG performed 10 repetitions of each of the two different exercises for the pectoralis major and triceps brachii. The MIPF, TMIF, RFP and AvgEMG of the pectoralis major (sternocostal part) and triceps brachii (long and lateral head) were measured before and immediately after the stretching protocols. A significant decrease in the MIPF from pre- to post-stretching was observed in both SG (p <0.001) and DG (p <0.05). No significant differences were found in the CG for all force parameters. No significant differences in the TMIF and RFP from pre- to post-stretching were found in the three groups. The SG showed a significant (p <0.05) decrease in the AvgEMG of the three muscles, whereas no significant differences were found for the DG and CG. These findings suggest that a low-volume static and dynamic stretching adversely affects efforts of muscle maximal strength of the upper limb muscles studied, but it does not seem to affect TMIF or RFP.
Visual search behaviours and verbal reports during film-based and in situ representative tasks in volleyball

Abstract Several researchers have explored the processes underlying perceptual-cognitive expertise, mainly using film-based studies. However, few have compared the extent to which data from film-based settings differ from those obtained through in situ collection. This gap in the literature is a relevant concern, since scientific research is used to provide guidance for designing training programmes. In this paper, eye movement recording and verbal reports of thinking were combined to explore the processes underpinning skilled performance in a representative volleyball task involving both film-based and in situ data collection. Nine volleyball players performed as backcourt defenders while wearing an eye-tracking device and providing verbal reports of thinking after each sequence. A number of significant differences were observed between the data gathered under film-based and in situ conditions. Namely, in the in situ condition participants employed longer fixations (728.11±129.27 ms) than in the film condition (659.57±178.06 ms), and there were differences in the nature of the fixation locations. With respect to verbal reports, participants exhibited superior level of sophistication in the in situ condition (2.57±0.50 vs. 2.30±0.84 in the film condition), while denoting a greater concern with the opponents under this condition (1.00±0.73) than in the film condition (0.59±0.60). These differences emerged despite task design and constraints being highly similar. No differences were apparent in the number of gaze fixations and fixation locations across conditions or in the number of verbalised condition concepts. Although exploratory, our data suggest that the mechanisms underpinning skilled decision-making in sports differ between film-based and in situ conditions.
College Baseball/Softball Periodized Torso Program

David J. Szymanski, MEd, CSCSGregory A. Fredrick, CSCSDepartment of Health and Human PerformanceAuburn UniversityKeywords: baseball; softball; periodization; torso; abdominals; low back.WHEN DESIGNING A SPORT-speciﬁc training program for base-ball/softball (BA/SB), it is impor-tant to implement a systematictotal body conditioning programthat will prepare the athlete for thedemands of the sport. A year-round periodized program shouldinclude a variety of upper- andlower-body exercises, and the in-tensity and volumes of exerciseshould change as the season ap-proaches. The exercises completedby the athletes should becomemore speciﬁc to the movementsinvolved in the sport. However,many BA/SB athletes perform tra-ditional trunk exercises that con-sist of continuous sets (rangingfrom 3 to 8 minutes) throughoutthe entire year. This type of repeti-tive torso training for the BA/SBathlete is not speciﬁc to the move-ments of the 2 sports, nor will itimprove the strength and power ofthe athletes. Torso movementsthat mimic the explosive, ballistic,and dynamic movements of swing-ing a bat or throwing a ball shouldbe performed instead.The purpose of this article is todescribe and illustrate how thestrength and conditioning special-ist or baseball/softball coach candevelop the powerful, twisting,and functional strength needed toimprove a college BA/SB player’sability to ﬁeld, throw, and hit. Ad-ditionally, this information shouldpositively affect injury risk andfurther educate those who aretraining for the explosive needs ofthe BA/SB athlete.
The impact of breathing on HRV measurements: Implications for the longitudinal follow-up of athletes

Abstract The purpose of the present work was to compare daily variations of heart rate variability (HRV) parameters between controlled breathing (CB) and spontaneous breathing (SB) sessions during a longitudinal follow-up of athletes. HRV measurements were performed daily on 10 healthy male runners for 21 consecutive days. The signals were recorded during two successive randomised 5-minutes sessions. One session was performed in CB and the other in SB. The results showed significant differences between the two respiration methods in the temporal, nonlinear and frequency domains. However, significant correlations were observed between CB and SB (higher than 0.70 for RMSSD and SD1), demonstrating that during a longitudinal follow-up, these markers provide the same HRV variations regardless of breathing pattern. By contrast, independent day-to-day variations were observed with HF and LF/HF frequency markers, indicating no significant relationship between SB and CB data over time. Therefore, we consider that SB and CB may be used for HRV longitudinal follow-ups only for temporal and nonlinear markers. Indeed, the same daily increases and decreases were observed whatever the breathing method employed. Conversely, frequency markers did not provide the same variations between SB and CB and we propose that these indicators are not reliable enough to be used for day-to-day HRV monitoring.
The effects of maximal and submaximal arm crank ergometry and cycle ergometry on postural sway

Abstract This study aimed to determine whether arm crank ergometry (ACE) disturbed postural sway to the same extent as cycle ergometry (CE). Nine healthy, none specifically trained adults undertook posturographic tests before and after five separate exercise trials consisting of: two incremental exercise tests to exhaustion for ACE and CE to examine postural sway responses to maximal exercise and to determine peak power output (Wmax); two subsequent tests of 30 min duration for ACE and CE at a relative workload corresponding to 50% of the ergometer-specific Wmax (ACErel; 53 ± 8 W and CErel; 109 ± 16 W). A final CE trial was performed at the same absolute power output (CEabs) as the submaximal ACE trial to match absolute exercise intensity (i.e., 53 ± 8 W). The centre of pressure (COP) displacement was recorded using a force platform before, immediately after exercise and during a 30-min recovery period. ACE had no effects on postural sway (P > 0.05). An increase in mediolateral COP displacement was observed following maximal CE only (P = 0.001), while anteroposterior COP displacement and COP path length increased following maximal and submaximal CE (P < 0.05). These differences in postural sway according to exercise mode likely stem from the activity of postural muscles when considering that CE recruits lower limb muscles involved in balance. This study provides evidence of an exercise mode which does not elicit post-exercise balance impairments, therefore possesses applications to those at an increased risk of falling.
Sleep/wake behaviours of elite athletes from individual and team sports

Abstract Sleep is an essential component for athlete recovery due to its physiological and psychological restorative effects, yet few studies have explored the habitual sleep/wake behaviour of elite athletes. The aims of the present study were to investigate the habitual sleep/wake behaviour of elite athletes, and to compare the differences in sleep between athletes from individual and team sports. A total of 124 (104 male, 20 female) elite athletes (mean ± s: age 22.2 ± 3.0 years) from five individual sports and four team sports participated in this study. Participants' sleep/wake behaviour was assessed using self-report sleep diaries and wrist activity monitors for a minimum of seven nights (range 7–28 nights) during a typical training phase. Mixed-effects analyses of variances were conducted to compare the differences in the sleep/wake behaviour of athletes from two sport types (i.e. individual and team). Overall, this sample of athletes went to bed at 22:59 ± 1.3, woke up at 07:15 ± 1.2 and obtained 6.8 ± 1.1 h of sleep per night. Athletes from individual sports went to bed earlier, woke up earlier and obtained less sleep (individual vs team; 6.5 vs 7.0 h) than athletes from team sports. These data indicate that athletes obtain well below the recommended 8 h of sleep per night, with shorter sleep durations existing among athletes from individual sports.
Rethinking fat as a fuel for endurance exercise

Abstract A key element contributing to deteriorating exercise capacity during physically demanding sport appears to be reduced carbohydrate availability coupled with an inability to effectively utilize alternative lipid fuel sources. Paradoxically, cognitive and physical decline associated with glycogen depletion occurs in the presence of an over-abundance of fuel stored as body fat that the athlete is apparently unable to access effectively. Current fuelling tactics that emphasize high-carbohydrate intakes before and during exercise inhibit fat utilization. The most efficient approach to accelerate the body’s ability to oxidize fat is to lower dietary carbohydrate intake to a level that results in nutritional ketosis (i.e., circulating ketone levels >0.5 mmol/L) while increasing fat intake for a period of several weeks. The coordinated set of metabolic adaptations that ensures proper interorgan fuel supply in the face of low-carbohydrate availability is referred to as keto-adaptation. Beyond simply providing a stable source of fuel for the brain, the major circulating ketone body, beta-hydroxybutyrate, has recently been shown to act as a signalling molecule capable of altering gene expression, eliciting complementary effects of keto-adaptation that could extend human physical and mental performance beyond current expectation. In this paper, we review these new findings and propose that the shift to fatty acids and ketones as primary fuels when dietary carbohydrate is restricted could be of benefit for some athletes.
A thorough assessment of benign genetic variability in GRN and MAPT

Mutations in APP, PSEN1, MAPTand GRNare the most common genetic causes of dementia. The previous miss‐assignment of pathogenicity to benign variants in these genes stresses the importance of discerning between disease causing mutations and benign variants with no pathogenic effect on the function of the respective protein. In this study we sequenced GRNand MAPTin 282 samples from the Centre d'Etude du Polymorphisme Humain ‐ Human Genome Diversity Cell Line Panel, in order to identify benign variants that could otherwise be mistaken for pathogenic mutations. We found sixteen different non‐synonymous changes, eleven of which are novel variants. © 2009 Wiley‐Liss, Inc.
The ubiquitin ligase CHIP/STUB1 targets mutant keratins for degradation

Keratin (K) intermediate filament proteins form cytoskeletal scaffolds in epithelia, the disruption of which leads to a large number of human disorders. KRT5 or KRT14 mutations cause epidermolysis bullosa simplex (EBS). The considerable intra‐ and interfamilial variability in EBS suggests modifying loci, most of which are unknown. In many human disorders, chaperones and the ubiquitin–proteasome system have been found to modify disease severity, thereby providing novel therapy targets. Here, we demonstrate upregulation of stress‐induced Hsp70 and Hsp90 in two EBS models, namely, in neonatal K5−/− mice and upon proteasome inhibition in cells that stably express the disease‐causing mutation K14–p.Arg125Cys, both harboring keratin aggregates. Furthermore, proteasome inhibition caused nuclear translocation of pHSF‐1 and an increase in K14–p.Arg125Cys‐positive aggregates in cells. Overexpression of the chaperone‐associated ubiquitin ligase CHIP/STUB1 strongly reduced keratin aggregates through increased degradation of mutant K14. Using CHIP–p.Met1_Ala142del (ΔTPR–CHIP), we demonstrated the involvement of Hsc70 and Hsp70 in mutant keratin degradation. Our data uncover common principles between EBS and other protein misfolding disorders, revealing that aggregation‐prone keratins are targeted by components of the chaperone machinery. Thus, modulation of the chaperone machinery using small molecules may represent a novel therapeutic strategy for dominant EBS, allowing reformation of an intact keratin cytoskeleton. Hum Mutat 31:466–476, 2010. © 2010 Wiley‐Liss, Inc.
Asymmetry analysis of the arm segments during forward handspring on floor

Abstract Asymmetry in gymnastics underpins successful performance and may also have implications as an injury mechanism; therefore, understanding of this concept could be useful for coaches and clinicians. The aim of this study was to examine kinematic and external kinetic asymmetry of the arm segments during the contact phase of a fundamental skill, the forward handspring on floor. Using a repeated single subject design six female National elite gymnasts (age: 19 ± 1.5 years, mass: 58.64 ± 3.72 kg, height: 1.62 ± 0.41 m), each performed 15 forward handsprings, synchronised 3D kinematic and kinetic data were collected. Asymmetry between the lead and non-lead side arms was quantified during each trial. Significant kinetic asymmetry was observed for all gymnasts (p < 0.005) with the direction of the asymmetry being related to the lead leg. All gymnasts displayed kinetic asymmetry for ground reaction force. Kinematic asymmetry was present for more gymnasts at the shoulder than the distal joints. These findings provide useful information for coaching gymnastics skills, which may subjectively appear to be symmetrical. The observed asymmetry has both performance and injury implications.
Functional evaluation of paraplegin mutations by a yeast complementation assay

An autosomal recessive form of hereditary spastic paraplegia (AR‐HSP) is primarily caused by mutations in the SPG7 gene, which codes for paraplegin, a subunit of the hetero‐oligomeric m‐AAA protease in mitochondria. In the current study, sequencing of the SPG7 gene in the genomic DNA of 25 unrelated HSP individuals/families led to the identification of two HSP patients with compound heterozygous mutations (p.G349S/p.W583C and p.A510V/p.N739KfsX741) in the coding sequence of the SPG7 gene. We used a yeast complementation assay to evaluate the functional consequence of novel SPG7 sequence variants detected in the HSP patients. We assessed the proteolytic activity of hetero‐oligomeric m‐AAA proteases composed of paraplegin variant(s) and proteolytically inactive forms of AFG3L2 (AFG3L2E575Q or AFG3L2K354A) upon expression in m‐AAA protease‐deficient yeast cells. We demonstrate that the newly identified paraplegin variants perturb the proteolytic function of hetero‐oligomeric m‐AAA protease. Moreover, commonly occurring silent polymorphisms such as p.T503A and p.R688Q could be distinguished from mutations (p.G349S, p.W583C, p.A510V, and p.N739KfsX741) in our HSP cohort. The yeast complementation assay thus can serve as a reliable system to distinguish a pathogenic mutation from a silent polymorphism for any novel SPG7 sequence variant, which will facilitate the interpretation of genetic data for SPG7. Hum Mutat 31:1–5, 2010. © 2010 Wiley‐Liss, Inc.