Subjective cognitive complaints in first episode psychosis: A focused follow-up on sex effect and alcohol usage.

A network of early psychosis-specific intervention programs at the University of Montreal in Montreal, Quebec, Canada, conducted a longitudinal naturalistic five-year study at two Urban Early Intervention Services (EIS). In this study, 198 patients were recruited based on inclusion/exclusion criteria and agreed to participate. Our objectives were to assess the subjective cognition complaints of schizophrenic patients assessed by Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) in their first-episode psychosis (FEP) in relation to their general characteristics. We also wanted to assess whether there are sex-based differences in the subjective cognitive complaints, as well as differences in cognitive complaints among patients who use alcohol in comparison to those who are abstainers. Additionally, we wanted to monitor the changes in the subjective complaints progress for a period of five years follow-up. Our findings showed that although women expressed more cognitive complaints than men [mean (SD) SSTICS, 28.2 (13.7) for women and 24.7 (13.2) for men], this difference was not statistically significant (r = -0.190, 95 % CI, -0. 435 to 0. 097). We also found that abstainers complained more about their cognition than alcohol consumers [mean (SD) SSTICS, 27.9 (13.4) for abstainers and 23.7 (12.9) for consumers], a difference which was statistically significant (r = -0.166, 95 % CI, -0. 307 to -0.014). Our findings showed a drop in the average score of SSTICS through study follow-up time among FEP patients. In conclusion, we suggest that if we want to set up a good cognitive remediation program, it is useful to start with the patients' demands. This demand can follow the patients' complaints. Further investigations are needed in order to propose different approaches between alcohol users and abstinent patients concerning responding to their cognitive complaints.

How physical activity behavior affected well-being, anxiety and sleep quality during COVID-19 restrictions in Iran.

OBJECTIVE: The Islamic Republic of Iran has displayed one of the highest rates of COVID-19 infection in the world and the highest rate of mortality in the Middle East. Iran has used a stringent package of preventive health measures to mitigate the spread of infection, which however has negatively affected individuals' physical and psychological health. This study aimed at examining whether physical-activity (PA) behavior, anxiety, well-being, and sleep-quality changed in response to the COVID-19-related public health restrictions enforced in Iran. PATIENTS AND METHODS: An online questionnaire was disseminated to adults residing in Iran from November 17, 2020, to February 13, 2021 (~88 days), during Iran's strictest public health restrictions. Main outcome measures included Godin-Shephard Leisure-Time Exercise Questionnaire, General Anxiety Disorder-7, Mental Health Continuum-Short Form, and Pittsburgh Sleep Quality Index. RESULTS: A total of 3,323 adults (mean age 30±11 years, 54.3% female) participated in the survey. Firstly, the restrictions generally reduced PA behavior: (a) among inactive participants (IPs), 60.6% became less active vs. 5.1% who became more active; and (b) among active participants (APs), 49.9% became less active vs. 22.8% who became more active. Secondly, PA behavior was associated with higher well-being and sleep quality during the restrictions: (a) APs reported higher (or lower) levels of well-being and sleep quality (or anxiety) than did IPs; and (b) among IPs as well as among APs, the more active the participants, the greater (or lower) the levels of well-being and sleep quality (or anxiety). CONCLUSIONS: This study showed the beneficial role of PA behavior for well-being, anxiety, and sleep quality during the COVID-19 restrictions, whereas such restrictions appeared to decrease PA participation. Active lifestyle should be then encouraged during the COVID-19 outbreak while taking precautions.

Predictors of Excess Patient Radiation Exposure During Chronic Total Occlusion Coronary Intervention: Insights From a Contemporary Multicentre Registry.

BACKGROUND: High patient radiation dose during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) might lead to procedural failure and radiation skin injury. METHODS: We examined the association between several clinical and angiographic variables on patient air kerma (AK) radiation dose among 748 consecutive CTO PCIs performed at 9 experienced US centres between May 2012 and May 2015. RESULTS: The mean age was 65 ± 10 years, 87% of patients were men, and 35% had previous coronary artery bypass graft surgery (CABG). Technical and procedural success was 92% and 90%, respectively. The median patient AK dose was 3.40 (interquartile range, 2.00-5.40) Gy and 34% of the patients received > 4.8 Gy (high radiation exposure). In univariable analysis male sex (P = 0.016), high body mass index (P < 0.001), history of hyperlipidemia (P = 0.023), previous CABG (P < 0.001), moderate or severe calcification (P < 0.001), tortuosity (P < 0.001), proximal cap ambiguity (P = 0.001), distal cap at a bifurcation (P = 0.006), longer CTO occlusion length (P < 0.001), blunt/no blunt stump (P < 0.001), and centre (P < 0.001) were associated with higher patient AK dose. In multivariable analysis high body mass index (P < 0.001), previous CABG (P = 0.005), moderate or severe calcification (P = 0.005), longer CTO occlusion length (P < 0.001), and centre (P < 0.001) were independently associated with higher patient AK dose. CONCLUSIONS: Approximately 1 in 3 patients who undergo CTO PCI receive high AK radiation dose (> 4.8 Gy). Several baseline clinical and angiographic characteristics can help predict the likelihood of high radiation dose and assist with intensifying efforts to reduce radiation exposure for the patient and the operator.

Guidewire and microcatheter utilization patterns during antegrade wire escalation in chronic total occlusion percutaneous coronary intervention: Insights from a contemporary multicenter registry.

OBJECTIVES: We sought to describe contemporary guidewire and microcatheter utilization for antegrade wire escalation (AWE) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: Equipment utilization for AWE has been variable and evolving over time. METHODS: We examined device utilization during 694 AWE attempts in 679 patients performed at 15 experienced US centers between May 2012 and April 2015. RESULTS: Mean age was 65.6 ± 9.7 years, and 85% of the patients were men. Successful wiring occurred in 436 AWE attempts (63%). Final technical and procedural success was 91% and 89%, respectively. The mean number of guidewire types used for AWE was 2.2 ± 1.4. The most frequently used guidewire types were the Pilot 200 (Abbott Vascular, 56% of AWE procedures), Fielder XT (Asahi Intecc, 45%), and the Confianza Pro 12 (Asahi Intecc, 28%). The same guidewires were the ones that most commonly crossed the occlusion: Pilot 200 (36% of successful AWE crossings), Fielder XT (20%), and Confianza Pro 12 (11%). A microcatheter or over-the-wire balloon was used for 81% of AWE attempts; the Corsair microcatheter (Asahi Intecc) was the most commonly used (44%). No significant association was found between guidewire type and incidence of major adverse cardiac events (MACE). CONCLUSIONS: Our contemporary, multicenter CTO PCI registry demonstrates that the most commonly used wires for AWE are polymer-jacketed guidewires. "Stiff" and polymer-jacketed guidewires appear to provide high crossing rates without an increase in MACE or perforation, and may thus be considered for upfront use. © 2016 Wiley Periodicals, Inc.

Accuracy of remote chest X-ray interpretation using Google Glass technology.

OBJECTIVES: We sought to explore the accuracy of remote chest X-ray reading using hands-free, wearable technology (Google Glass, Google, Mountain View, California). METHODS: We compared interpretation of twelve chest X-rays with 23 major cardiopulmonary findings by faculty and fellows from cardiology, radiology, and pulmonary-critical care via: (1) viewing the chest X-ray image on the Google Glass screen; (2) viewing a photograph of the chest X-ray taken using Google Glass and interpreted on a mobile device; (3) viewing the original chest X-ray on a desktop computer screen. One point was given for identification of each correct finding and a subjective rating of user experience was recorded. RESULTS: Fifteen physicians (5 faculty and 10 fellows) participated. The average chest X-ray reading score (maximum 23 points) as viewed through the Google Glass, Google Glass photograph on a mobile device, and the original X-ray viewed on a desktop computer was 14.1±2.2, 18.5±1.5 and 21.3±1.7, respectively (p<0.0001 between Google Glass and mobile device, p<0.0001 between Google Glass and desktop computer and p=0.0004 between mobile device and desktop computer). Of 15 physicians, 11 (73.3%) felt confident in detecting findings using the photograph taken by Google Glass as viewed on a mobile device. CONCLUSION: Remote chest X-ray interpretation using hands-free, wearable technology (Google Glass) is less accurate than interpretation using a desktop computer or a mobile device, suggesting that further technical improvements are needed before widespread application of this novel technology.

Impact of crossing technique on the incidence of periprocedural myocardial infarction during chronic total occlusion percutaneous coronary intervention.

OBJECTIVES: We sought to evaluate the impact of crossing strategy on the incidence of periprocedural myocardial infarction (PMI) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The optimal technique for crossing coronary CTOs remains controversial. METHODS: We retrospectively examined the incidence of PMI among 184 consecutive patients who underwent CTO PCI at our institution between 2012 and 2015. Creatine kinase-myocardial band fraction (CK-MB) and troponin were measured before and after PCI in all patients. PMI was defined as CK-MB increase ≥3× upper limit of normal (ULN). RESULTS: Mean age was 65 ± 8 years, 98% of patients were men, 57% had diabetes mellitus, 36% were current smokers, 38% had prior heart failure, 31% had prior coronary artery bypass graft surgery (CABG), and 55% had prior PCI. The retrograde approach was used in 38% of cases. As compared with antegrade wire escalation and antegrade dissection/re-entry, use of the retrograde approach was associated with higher J-CTO (Multicenter CTO Registry of Japan) scores (P < 0.0001), higher frequency of moderate or severe calcification (P = 0.0061), longer CTO length (P < 0.0001), more frequent proximal cap ambiguity (P < 0.0001), and lower technical (P = 0.0007) and procedural (P = 0.0014) success. The frequency of PMI for the antegrade-only and retrograde cases was 10% and 33%, respectively (P = 0.0001). On multivariate analysis, use of the retrograde approach and moderate/severe calcification were independently associated with higher incidence of PMI. CONCLUSIONS: As compared with antegrade-only crossing techniques, the retrograde approach is used in patients with more complex anatomy but may carry higher risk for PMI. © 2016 Wiley Periodicals, Inc.

Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score.

OBJECTIVES: This study sought to develop a novel parsimonious score for predicting technical success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) performed using the hybrid approach. BACKGROUND: Predicting technical success of CTO PCI can facilitate clinical decision making and procedural planning. METHODS: We analyzed clinical and angiographic parameters from 781 CTO PCIs included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) using a derivation and validation cohort (2:1 sampling ratio). Variables with strong association with technical success in multivariable analysis were assigned 1 point, and a 4-point score was developed from summing all points. The PROGRESS CTO score was subsequently compared with the J-CTO (Multicenter Chronic Total Occlusion Registry in Japan) score in the validation cohort. RESULTS: Technical success was 92.9%. On multivariable analysis, factors associated with technical success included proximal cap ambiguity (beta coefficient [b] = 0.88), moderate/severe tortuosity (b = 1.18), circumflex artery CTO (b = 0.99), and absence of "interventional" collaterals (b = 0.88). The resulting score demonstrated good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow chi-square = 2.633; p = 0.268, and receiver-operator characteristic [ROC] area = 0.778) and validation (Hosmer-Lemeshow chi-square = 5.333; p = 0.070, and ROC area = 0.720) subset. In the validation cohort, the PROGRESS CTO and J-CTO scores performed similarly in predicting technical success (ROC area 0.720 vs. 0.746, area under the curve difference = 0.026, 95% confidence interval = -0.093 to 0.144). CONCLUSIONS: The PROGRESS CTO score is a novel useful tool for estimating technical success in CTO PCI performed using the hybrid approach.

The impact of percutaneous coronary intervention of chronic total occlusions on left ventricular function and clinical outcomes.

A meta-analysis by Hoebers et al. reported that successful chronic total occlusion (CTO) recanalization resulted in an increase in left ventricular (LV) ejection fraction by 4.44% (P<0.01) and a reduction in LV end-diastolic volume by 6.14 mL/m(2) during follow-up as compared with baseline, suggesting beneficial LV remodeling. These findings are important as the myocardium supplied by a CTO frequently has sustained irreversible injury and further support the clinical benefits of CTO interventions.

Application and outcomes of a hybrid approach to chronic total occlusion percutaneous coronary intervention in a contemporary multicenter US registry.

BACKGROUND: A hybrid approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) prioritizing and combining all available crossing techniques was developed to optimize procedural efficacy, efficiency, and safety, but there is limited published data on its outcomes. METHODS: We examined the procedural techniques and outcomes of 1036 consecutive CTO PCIs performed using a hybrid approach between 2012 and 2015 at 11 US centers. RESULTS: Mean age was 65 ± 10 years and 86% of the patients were men, with a high prevalence of diabetes mellitus (43%) and prior coronary artery bypass graft surgery (34%). Most target CTOs were located in the right coronary artery (59%), followed by the left anterior descending artery (23%) and the circumflex (19%). Dual injection was used in 71%. Technical success was achieved in 91% and a major procedural complication occurred in 1.7% of cases. The final successful crossing technique was antegrade wire escalation in 46%, antegrade dissection/re-entry in 26%, and retrograde in 28%. The initial crossing strategy was successful in 58% of the lesions, whereas 39% required an additional approach. Overall, antegrade wire escalation was used in 71%, antegrade dissection/re-entry in 36%, and the retrograde approach in 42% of procedures. Median contrast volume, fluoroscopy time, and air kerma radiation dose were 260 (200-360) ml, 44 (27-72) min, and 3.4 (2.0-5.4) Gray, respectively. CONCLUSION: Application of a hybrid approach to CTO crossing resulted in high success and low complication rates across a varied group of operators and hospital practice structures, supporting its expanding use in CTO PCI.

Analyses of hypomethylated oil palm gene space.

Demand for palm oil has been increasing by an average of ∼8% the past decade and currently accounts for about 59% of the world's vegetable oil market. This drives the need to increase palm oil production. Nevertheless, due to the increasing need for sustainable production, it is imperative to increase productivity rather than the area cultivated. Studies on the oil palm genome are essential to help identify genes or markers that are associated with important processes or traits, such as flowering, yield and disease resistance. To achieve this, 294,115 and 150,744 sequences from the hypomethylated or gene-rich regions of Elaeis guineensis and E. oleifera genome were sequenced and assembled into contigs. An additional 16,427 shot-gun sequences and 176 bacterial artificial chromosomes (BAC) were also generated to check the quality of libraries constructed. Comparison of these sequences revealed that although the methylation-filtered libraries were sequenced at low coverage, they still tagged at least 66% of the RefSeq supported genes in the BAC and had a filtration power of at least 2.0. A total 33,752 microsatellites and 40,820 high-quality single nucleotide polymorphism (SNP) markers were identified. These represent the most comprehensive collection of microsatellites and SNPs to date and would be an important resource for genetic mapping and association studies. The gene models predicted from the assembled contigs were mined for genes of interest, and 242, 65 and 14 oil palm transcription factors, resistance genes and miRNAs were identified respectively. Examples of the transcriptional factors tagged include those associated with floral development and tissue culture, such as homeodomain proteins, MADS, Squamosa and Apetala2. The E. guineensis and E. oleifera hypomethylated sequences provide an important resource to understand the molecular mechanisms associated with important agronomic traits in oil palm.

Identification and expression of a novel transcript of the growth and differentiation factor-11 gene.

The growth and differentiation factor-11 (GDF-11) gene is thought to code for a single protein that plays a crucial role in regulating the development of multiple tissues. In this study, we aimed to investigate if the GDF-11 gene has another transcript and, if so, to characterise this transcript and determine its tissue-specific and developmental expression. We have identified a novel transcript of GDF-11 in mouse muscle, which contains the 3' region of intron 1, exon 2, exon 3 and 3'UTR, and has two transcription initiation sites and a single termination site. We named the novel transcript GDF-11ΔEx1 because it does not contain exon 1 of canonical GDF-11. The GDF-11ΔEx1 transcript was expressed in the skeletal muscles, heart, brain and kidney, but was undetectable in the liver and gut. The concentration of the GDF-11ΔEx1 transcript was increased in gastrocnemius muscles from three to 6 weeks of age, a period of accelerated muscle growth, steadily declined thereafter and was higher in male than female mice (P < 0.001 for age and sex). GDF-11ΔEx1 cDNA was predicted to code for a putative N-terminal-truncated propeptide and the canonical ligand for GDF-11. However, propeptide-specific antibodies could not identify proteins of the expected size in skeletal muscle. Interestingly, in silico analysis of the GDF-11ΔEx1 RNA predicted a secondary structure with the potential to coordinate multiple protein interactions as a molecular scaffold. Therefore, we postulate that GDF-11ΔEx1 may act as a long non-coding RNA to regulate the transcription of canonical GDF-11 and/or other genes in skeletal muscle and other tissues.

Mapping, phylogenetic and expression analysis of the RNase (RNase A) locus in cattle.

The mammalian secreted ribonucleases (RNases) comprise a large family of structurally related proteins displaying considerable sequence variation, and have been used in evolutionary studies. RNase 1 (RNase A) has been assumed to play a role in digestion, while other members have been suggested to contribute to host defence. Using the recently assembled bovine genome sequence, we characterised the complete repertoire of genes present in the RNaseA family locus in cattle, and compared this with the equivalent locus in the human and mouse genomes. Several additions and corrections to the earlier analysis of the RNase locus in the mouse genome are presented. The bovine locus encodes 19 RNases, of which only six have unambiguous equivalent genes in the other two species. Chromosomal mapping and phylogenetic analysis indicate that a number of distinct gene duplication events have occurred in the cattle lineage since divergence from the human and mouse lineages. Substitution analysis suggests that some of these duplicated genes are under evolutionary pressure for purifying selection and may therefore be important to the physiology of cattle. Expression analysis revealed that individual RNases have a wide pattern of expression, including diverse mucosal epithelia and immune-related cells and tissues. These data clarify the full repertoire of bovine RNases and their relationships to those in humans and mice. They also suggest that RNase gene duplication within the bovine lineage accompanied by altered tissue-specific expression has contributed a survival advantage.

The BPI-like/PLUNC family proteins in cattle.

Members of the protein family having similarity to BPI (bactericidal/permeability increasing protein) (the BPI-like proteins), also known as the PLUNC (palate, lung and nasal epithelium clone) family, have been found in a range of mammals; however, those in species other than human or mouse have been relatively little characterized. Analysis of the BPI-like proteins in cattle presents unique opportunities to investigate the function of these proteins, as well as address their evolution and contribution to the distinct physiology of ruminants. The present review summarizes the current understanding of the nature of the BPI-like locus in cattle, including the duplications giving rise to the multiple BSP30 (bovine salivary protein 30 kDa) genes from an ancestral gene in common with the single PSP (parotid secretory protein) gene found in monogastric species. Current knowledge of the expression of the BPI-like proteins in cattle is also presented, including their pattern of expression among tissues, which illustrate their independent regulation at sites of high pathogen exposure, and the abundance of the BSP30 proteins in saliva and salivary tissues. Finally, investigations of the function of the BSP30 proteins are presented, including their antimicrobial, lipopolysaccharide-binding and bacterial aggregation activities. These results are discussed in relation to hypotheses regarding the physiological role of the BPI-like proteins in cattle, including the role they may play in host defence and the unique aspects of digestion in ruminants.

Annotation of sheep keratin intermediate filament genes and their patterns of expression.

Keratin IF (KRT) and keratin-associated protein genes encode the majority of wool and hair proteins. We have identified cDNA sequences representing nine novel sheep KRT genes, increasing the known active genes from eight to 17, a number comparable to that in the human. However, the absence of KRT37 in the type I family and the discovery of type II KRT87 in sheep exemplify species-specific compositional differences in hair KRT genes. Phylogenetic analysis of hair KRT genes within type I and type II families in the sheep, cattle and human genomes revealed a high degree of consistency in their sequence conservation and grouping. However, there were differences in the fibre compartmentalisation and keratinisation zones for the expression of six ovine KRT genes compared with their human orthologs. Transcripts of three genes (KRT40, KRT82 and KRT84) were only present in the fibre cuticle. KRT32, KRT35 and KRT85 were expressed in both the cuticle and the fibre cortex. The remaining 11 genes (KRT31, KRT33A, KRT33B, KRT34, KRT36, KRT38-39, KRT81, KRT83 and KRT86-87) were expressed only in the cortex. Species-specific differences in the expressed keratin gene sets, their relative expression levels and compartmentalisation are discussed in the context of their underlying roles in wool and hair developmental programmes and the distinctive characteristics of the fibres produced.

Epigenetic regulation of milk production in dairy cows.

It is well established that milk production of the dairy cow is a function of mammary epithelial cell (MEC) number and activity and that these factors can be influenced by diverse environmental influences and management practises (nutrition, milk frequency, photoperiod, udder health, hormonal and local effectors). Thus, understanding how the mammary gland is able to respond to these environmental cues provides a huge potential to enhance milk production of the dairy cow. In recent years our understanding of molecular events within the MEC underlying bovine lactation has been advanced through mammary microarray studies and will be further advanced through the recent availability of the bovine genome sequence. In addition, the potential of epigenetic regulation (non-sequence inheritable chemical changes in chromatin, such as DNA methylation and histone modifications, which affect gene expression) to manipulate mammary function is emerging. We propose that a substantial proportion of unexplained phenotypic variation in the dairy cow is due to epigenetic regulation. Heritability of epigenetic marks also highlights the potential to modify lactation performance of offspring. Understanding the response of the MEC (cell signaling pathways and epigenetic mechanisms) to external stimuli will be an important prerequisite to devising new technologies for maximising their activity and, hence, milk production in the dairy cow.

Combined effect of resting heart rate and physical activity on ischaemic heart disease: mortality follow-up in a population study (the HUNT study, Norway).

BACKGROUND: The combined effect of resting heart rate (RHR) and physical activity (PA) on ischaemic heart disease (IHD) has never been assessed. The objective of this study was to assess the association of RHR with IHD mortality, and to evaluate the potentially modifying effect of PA on this association. METHODS: In a prospective cohort study of 24 999 men and 25 089 women free from cardiovascular disease at baseline, Cox proportional hazard models were used to estimate adjusted hazard ratios of death from IHD related to RHR measured at baseline. The combined effect of RHR and self-reported PA on the risk of death from IHD was also assessed. RESULTS: During a mean of 18.2 (SD 4) years of follow-up, 2566 men and 1814 women died from cardiovascular causes. For each increment of 10 heart beats per minute, risk of death from IHD was 18% higher in women <70 years of age (p<0.001); no such association was observed among women > or =70 years. Among men, there was a corresponding 10% higher risk in the younger (p = 0.004), and 11% higher risk in the older age group (p = 0.01). Among women, the risk associated with high RHR was substantially attenuated in those who reported a high level of PA, whereas in men, there was no clear indication that PA could modify the positive effect of RHR. CONCLUSION: RHR is positively associated with the risk of death from IHD, and among women, the results suggest that by engaging in PA, the risk associated with a high RHR may be substantially reduced.

The bovine lactation genome: insights into the evolution of mammalian milk.

BACKGROUND: The newly assembled Bos taurus genome sequence enables the linkage of bovine milk and lactation data with other mammalian genomes. RESULTS: Using publicly available milk proteome data and mammary expressed sequence tags, 197 milk protein genes and over 6,000 mammary genes were identified in the bovine genome. Intersection of these genes with 238 milk production quantitative trait loci curated from the literature decreased the search space for milk trait effectors by more than an order of magnitude. Genome location analysis revealed a tendency for milk protein genes to be clustered with other mammary genes. Using the genomes of a monotreme (platypus), a marsupial (opossum), and five placental mammals (bovine, human, dog, mice, rat), gene loss and duplication, phylogeny, sequence conservation, and evolution were examined. Compared with other genes in the bovine genome, milk and mammary genes are: more likely to be present in all mammals; more likely to be duplicated in therians; more highly conserved across Mammalia; and evolving more slowly along the bovine lineage. The most divergent proteins in milk were associated with nutritional and immunological components of milk, whereas highly conserved proteins were associated with secretory processes. CONCLUSIONS: Although both copy number and sequence variation contribute to the diversity of milk protein composition across species, our results suggest that this diversity is primarily due to other mechanisms. Our findings support the essentiality of milk to the survival of mammalian neonates and the establishment of milk secretory mechanisms more than 160 million years ago.

Expression patterns of keratin intermediate filament and keratin associated protein genes in wool follicles.

The catalogue of hair keratin intermediate filaments (KIFs) and keratin-associated proteins (KAPs) present in wool follicles is incomplete. The full coding sequences for three novel sheep KIFs (KRT27, KRT35 and KRT38) and one KAP (KRTAP4-3) were established in this study. Spatial expression patterns of these and other genes (KRT31, KRT85, KRTAP6-1 and trichohyalin) were determined by in situ hybridisation in wool follicles at synchronised stages of growth. Transcription proceeded in the order: trichohyalin, KRT27, KRT85, KRT35, KRT31, KRT38, KRTAP6-1 and KRTAP4-3, as determined by increasing distance of their expression zones from the germinal matrix in anagen follicles. Expression became gradually more restricted to the lower follicle during follicle regression (catagen), and ceased during dormancy (telogen). Some genes (KRT27, KRT31, KRT85 and KRTAP6-1), but not others, were expressed in cortical cells forming the brush-end, indicating specific requirements for the formation of this anchoring structure. The resumption of keratin expression was observed only in later stages of follicle reactivation (proanagen). KIF expression patterns in primary wool follicles showed general resemblance to their human homologues but with some unique features. Consistent differences in localisation between primary and secondary wool follicles were observed. Asymmetrical expression of KRT27, KRT31, KRT35, KRT85 and trichohyalin genes in secondary follicles were associated with bulb deflection and follicle curvature, suggesting a role in the determination of follicle and fibre morphology.