Miracle-dz/UniFAR-FTUs huggingface dataset:
Injury‐induced maladaptation and dysregulation of calcium channel α2δ subunit proteins and its contribution to neuropathic pain development

Voltage‐gated calcium channels (VGCCs) play important roles in physiological functions including the modulation of neurotransmitter release, neuronal network activities, intracellular signalling pathways and gene expression. Some pathological conditions, including nerve injuries, can cause the dysregulation of VGCCs and their subunits. This in turn can lead to a functional maladaptation of VGCCs and their subunits, which can contribute to the development of disorders such as pain sensations. This review has summarized recent findings related to maladaptive changes in the dysregulated VGCC α2δ1 subunit (Cavα2δ1) with a focus on exploring the mechanisms underlying the contribution of Cavα2δ1 to pain signal transduction. At least under neuropathic pain conditions, the dysregulated Cavα2δ1 can modulate VGCC functions as well as other plasticity changes. The latter includes abnormal excitatory synaptogenesis resulting from its interactions with injury‐induced extracellular matrix glycoprotein molecule thrombospondins, which is independent of the VGCC functions. Blocking Cavα2δ1 with gabapentinoids can reverse neuropathic pain significantly with relatively mild side effects, but only in a small population of neuropathic pain patients due to reasons yet to be explored. There are emerging data suggesting that early preventive treatment with gabapentinoids can prevent aberrant excitatory synapse formation and the development of chronic pain. If these findings are confirmed clinically, this could be an attractive approach for neuropathic pain management.
Shifts in hatch dates do not provide pied flycatchers with a rapid ontogenetic route to adjust offspring time schedules to climate change

Environments change rapidly, and it is unclear whether organisms with complex life-styles, such as avian migrants, are able to adjust sufficiently. For understanding human impacts on ecosystem functioning, it is crucial to understand how well, and by which mechanisms species are able to adapt. To improve the understanding of migrants’ ability to adjust their annual timing to climate change, we investigated ontogenetic hatch date effects on adult spring migration timing and female egg-laying dates. We experimentally delayed hatch dates of pied flycatchers Ficedula hypoleuca by 1 week in three breeding seasons by delaying incubation onset. We investigated if natural and experimental (shifts in) hatch date affected timing of recruiting individuals up to at least 3 years after the manipulation. Spring arrival dates were positively correlated with natural variation in hatch dates in three of the 5 years considered, but no such effects were found in egg laying. Experiments showed that delayed hatching resulted in delayed arrival and laying only in 1-year-old and not in older birds. These effects were mostly observed during one of the study years. The discrepancy between experimental and natural hatch date effects indicates that a causal hatch date effect is not generally responsible for the correlation between a birds’ birth date and timing during adulthood. Instead, we propose that natural hatch date effects on spring arrival arise from genetic variation in migration schedules, while delays in hatching induced carry-over effects on arrival and laying dates in offspring (e.g. the experimental effect in 2010). Strong support for year-specific expression of hatch date and delay effects on time schedules imply that trait-variation can be easily obscured. The latter may explain the lack of hatch date effects on female egg laying. Our results imply that plasticity in breeding phenology does not provide pied flycatchers with a non-genetic inheritance route to rapidly advance annual cycles. Instead, plasticity may rather masks (genetic) trait-variation for selection to act on, and thereby slow down micro-evolutionary adaptation to changing environments. A plain language summary is available for this article.
'DNA Strider': a 'C' program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers.

DNA Strider is a new integrated DNA and Protein sequence analysis program written with the C language for the Macintosh Plus, SE and II computers. It has been designed as an easy to learn and use program as well as a fast and efficient tool for the day-to-day sequence analysis work. The program consists of a multi-window sequence editor and of various DNA and Protein analysis functions. The editor may use 4 different types of sequences (DNA, degenerate DNA, RNA and one-letter coded protein) and can handle simultaneously 6 sequences of any type up to 32.5 kB each. Negative numbering of the bases is allowed for DNA sequences. All classical restriction and translation analysis functions are present and can be performed in any order on any open sequence or part of a sequence. The main feature of the program is that the same analysis function can be repeated several times on different sequences, thus generating multiple windows on the screen. Many graphic capabilities have been incorporated such as graphic restriction map, hydrophobicity profile and the CAI plot- codon adaptation index according to Sharp and Li. The restriction sites search uses a newly designed fast hexamer look-ahead algorithm. Typical runtime for the search of all sites with a library of 130 restriction endonucleases is 1 second per 10,000 bases. The circular graphic restriction map of the pBR322 plasmid can be therefore computed from its sequence and displayed on the Macintosh Plus screen within 2 seconds and its multiline restriction map obtained in a scrolling window within 5 seconds.
Cooperative turbo coding with time-varying rayleigh fading channels

In a cooperative transmission system, a source cooperates with a relay to transmit a message to a local destination. This paper proposes an adaptive cooperative protocol utilizing turbo codes and studies the trade-off between spatial and temporal diversity in increasingly mobile channels. While the advantage of cooperation is most pronounced in slow fading channels—on the order of 8-12 dB for the system considered here—the benefit gradually decreases with increasing mobility and vanishes at a normalized Doppler spread of 10 –2. Nevertheless, for typical wireless packet data services, cooperative coding can provide appreciable gain even in moderately mobile environments (e.g., up to 50 km/h). While the protocol implicitly adapts to varying channel conditions, adaptivity based on explicit knowledge of channel state information is also considered, and we find that the adaptive choice of two relays reduces the power requirement in half.
The translation start signal region of TEM beta-lactamase mRNA is responsible for heat shock-induced repression of amp gene expression in Escherichia coli

pBR322 contains the amp gene encoding beta-lactamase. When Escherichia coli carrying this plasmid is exposed to heat shock, beta-lactamase synthesis is repressed transiently at the translational level. To identify the DNA element responsible for this translational repression, DNA segments containing the translation start region of the amp gene were excised from pAT153 and fused in frame with the lacZ reading frame in the open reading frame vector pORF1. These constructs were introduced into E. coli, and the effect of heat shock of the cells on the synthesis of beta-galactosidase starting from the amp start codon was examined. As is the case for pBR322-encoded synthesis of beta-lactamase, the synthesis of beta-galactosidase encoded by the fused genes also ceased transiently upon heat shock. It is concluded that the heat shock-induced repression of the amp gene occurs at the initiation step of translation. As far as the present study is concerned, the minimum DNA segment responsible for the repression is AT TGA AAA AGG AAG AGT ATG AG, which includes the Shine-Dalgarno sequence (AAGGA) and the initiation codon (ATG).
Bidirectional pattern‐specific plasticity of the slow afterhyperpolarization in rats: role for high‐voltage activated Ca2+ channels and Ih

A burst of action potentials in hippocampal neurons is followed by a slow afterhyperpolarization (sAHP) that serves to limit subsequent firing. A reduction in the sAHP accompanies acquisition of several types of learning, whereas increases in the sAHP are correlated with cognitive impairment. The present study demonstrates in vitro that activity‐dependent bidirectional plasticity of the sAHP does not require synaptic activation, and depends on the pattern of action potential firing. Whole‐cell current‐clamp recordings from CA1 pyramidal neurons in hippocampal slices from young rats (postnatal days14–24) were performed in blockers of synaptic transmission. The sAHP was evoked by action potential firing at gamma‐related (50 Hz, gamma‐AHP) or theta frequencies (5 Hz, theta‐AHP), two firing frequencies implicated in attention and memory. Interestingly, when the gamma‐AHP and theta‐AHP were evoked in the same cell, a gradual potentiation of the gamma‐AHP (186 ± 31%) was observed that was blocked using Ca2+ channel blockers nimodipine (10 μm) or ω‐conotoxin MVIIC (1 μm). In experiments that exclusively evoked the sAHP with 50 Hz firing, the gamma‐AHP was similarly potentiated (198 ± 44%). However, theta‐burst firing pattern alone resulted in a decrease (65 ± 19%) of the sAHP. In these experiments, application of the h‐channel blocker ZD7288 (25 μm) selectively prevented enhancement of the gamma‐AHP. These data demonstrate that induction requirements for bidirectional AHP plasticity depend on the pattern of action potential firing, and result from distinct mechanisms. The identification of novel mechanisms underlying AHP plasticity in vitro provides additional insight into the dynamic processes that may regulate neuronal excitability during learning in vivo.
Immunoglobulin class and IgG subclass distribution of anticardiolipin antibodies in patients with systemic lupus erythematosus and associated disorders

The class and subclass distribution of an antibody response may give insight into the stimulating mechanism and likely effector functions. IgA, IgG and IgM anlicardiolipin antibodies (aCL) were quantified in a consecutive series of 200 samples sent to an autoimmune serology laboratory to determine the relationships between aCL responses of each of these antibody classes and, in particular, whether there was any utility in the measurement of IgA aCL. Positive results for one of the three aCL isotypes were found in 105 samples (53%). and in 41 samples IgA aCL was detected (21%). However, amongst these unselected samples, little additional information was obtained by measurement of IgA aCL, which was found in conjunction with IgM or IgG aCL in all but five samples, and in these the isolated elevation of IgA aCL was only slight, and showed no disease specificity. The levels of each of the four IgG subclasses of aCL were measured in a subgroup of serum samples from 28 patients with autoimmune disease and from 29 patients with syphilis. Amongst the SLE patients IgGl and lgG3 aCL were the predominant IgG subclasses, consistent with an antigen‐driven. T cell‐dependent antibody response. However, a subgroup of eight of the autoimmune subjects had predominant elevation of IgG2 aCL, possibly implying a role for T cell‐independent antibody production to cardiolipin. Amongst the syphilis patients IgG I and IgG3 aCL were also the predominant subclasses of aCL but lgG4 aCL were also detected in the majority of subjects, consistent with prolonged antigenic stimulation.
Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese.

BACKGROUND AND PURPOSE Angiotensin I-converting enzyme (ACE) gene deletion polymorphism (D) has recently been suggested as a significant risk factor for cerebrovascular disease in studies involving Japanese and white populations. We investigated the role of ACE D polymorphism in the pathogenesis of cerebrovascular disease in Taiwanese. METHODS To examine the association of ACE genotype and allele frequency with cerebrovascular disease, we conducted a study of 306 stroke patients and 300 control subjects matched by age and sex. RESULTS Although the frequencies of both the homozygous deletion (DD) genotype and the D allele were greater in stroke patients than in control subjects, these differences were not significant. Further comparison of the frequencies of the DD genotype and the D allele in the three stroke subgroups (intracerebral hemorrhage, probable large-vessel disease, and probable small-vessel lacunar infarction) with the control group revealed no significant associations. Moreover, ACE gene polymorphism was not significantly associated with age of onset of stroke. Stepwise logistic regression analysis of the presence of the D allele and data on risk factors confirmed the lack of significant association between ACE deletion polymorphism and cerebrovascular disease. Moreover, no association was identified between ACE genotypes and any of the relative risk factors for cerebral infarction or severity of carotid atherosclerosis. CONCLUSIONS Our results suggest that deletion polymorphism of the ACE gene is not associated with the pathogenesis of cerebrovascular disease in Taiwanese.
Assessment of Learner Metacognition in a Professional Pharmacy Elective Course

Objective. To investigate the effect of strategic feedback and metacognitive processes on learners’ ability to predict performance and improve self-awareness. Methods. Strategic faculty and peer feedback, as well as self-assessments, were implemented in a professional pharmacy elective course throughout the semester, focused on three case-based oral presentations. After each presentation, students utilized an objective rubric to determine self-predicted and peer-predicted scores. Actual scores from faculty were compared to students’ predicted scores. Results. Students’ ability to predict presentation scores did not improve over time; however, students were able to accurately estimate performance in certain rubric sections on individual presentations (depth of problem, presentation). Students were generally overconfident in predicting their performance. When broken down into tertiles, top performing students were more accurate in their self-assessments compared to bottom performing students. Bottom performing students were highly overconfident in their assessment. Conclusion. Self-awareness is essential for professionals, though difficult to cultivate and improve in one semester. Incorporating longitudinal, continuous feedback and metacognitive skills may help learners become more aware of their own performance and devise a plan for enhancement.
Relationship of Paternity Status, Welfare Reform Period, and Racial/Ethnic Disparities in Infant Mortality

The objective of this study was to examine the relationship of paternity status, welfare reform period, and racial/ethnic disparities in infant mortality. The study used retrospective analysis of birth outcomes data from singleton birth/infant death data in Milwaukee, Wisconsin, from 1993 to 2009. Multivariate logistic regression was used to examine the relationship between paternity status, welfare reform period, and infant mortality, adjusting for maternal and infant characteristics. Data consisted of almost 185,000 singleton live births and 1,739 infant deaths. Although unmarried women with no father on record made up about 32% of the live births, they accounted for over two thirds of the infant deaths compared with married women with established paternity who made up 39% of live births but had about a quarter of infant deaths. After adjustments, any form of paternity establishment was protective against infant mortality across all racial/ethnic groups. Unmarried women with no father on record had twice to triple the odds of infant mortality among all racial/ethnic groups. The likelihood of infant mortality was only significantly greater for African American women in the postwelfare (1999-2004; odds ratio = 1.27; 95% confidence interval = 1.10-1.46) period compared with the 1993 to 1998 period. Study findings suggest that any form of paternity establishment may have protective effect against infant mortality. Welfare reform changes may have reduced some of the protection against infant mortality among unmarried African American women that was present before the welfare legislation. Policies and programs that promote or support increased paternal involvement and establishment of paternity may improve birth outcomes and help reduce infant mortality.
Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: in defense of the Rotterdam criteria.

CONTEXT Polycystic ovary syndrome (PCOS) is a very common endocrinopathy with a heterogeneous presentation whose etiology is still uncertain. Not surprisingly, therefore, the definition of, and diagnostic criteria for, PCOS remain controversial. OBJECTIVE The objective of the study was to review and justify the basis for the recently revised definition of PCOS arising from the joint European Society for Human Reproduction & Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) Rotterdam workshop in 2003. INTERVENTION(S) The Rotterdam criteria take account of the broad spectrum of presenting features of PCOS, including women with hyperandrogenism but regular menses and, more controversially, those with menstrual disturbance without overt androgen excess. POSITIONS: The Rotterdam criteria for definition and diagnosis of PCOS, in the opinion of this author, represent a significant advance in recognizing the broad spectrum of presentation of the syndrome and acknowledge that the clinical and biochemical features may vary with time within individuals. The important refinements when compared to the 1990 NIH definition of PCOS are: 1) inclusion of polycystic ovarian morphology; and 2) inclusion of subjects with hirsutism and regular menses. CONCLUSIONS These new diagnostic criteria for PCOS reflect the significant advances, particularly from studies of familial PCOS, in understanding of the etiology of the syndrome and the basis for its heterogeneity. Under the revised diagnostic criteria, the inclusion of women with hyperandrogenism and regular cycles has met with general agreement. The inclusion of women with oligomenorrhea and polycystic ovaries who do not have clear evidence of androgen excess is, in the opinion of this author, also justified but remains a contentious issue and one that requires further investigation.
Gastrodin improves cognitive dysfunction and decreases oxidative stress in vascular dementia rats induced by chronic ischemia.

OBJECTIVE To study the potential protective effects of gastrodin on reducing tissue oxidative stress and attenuating cognitive deficits in vascular dementia induced by cerebral chronic hyperfusion. To explore the detailed molecular mechanisms. METHODS 6 to 8 week old male Wistar rats were adopted as experimental animals. Animals were divided into the following groups: Group 1 (sham group with no occlusion), Group 2 (control group with 2VO procedure), Group 3 (sham group with gastrodin administration), Group 4 (2VO group with gastrodin administration). Morris water maze (MWM) test was adopted to test the learning and memory function of rats within different groups. MDA, glutathione peroxidase and total thiol assessment was done to reflect the oxidative stress in the brain tissue. Cell counting kit-8 (CCK8) and flow cytometry (FCM) were performed to examine the cell viability and apoptosis rate of SH-SY5Y cells induced by hydrogen peroxide and rescued by gastrodin treatments. Reactive oxygen species (ROS) generation was determined by the 2', 7'-dichlorofluorescein diacetate (DCFH-DA) assay. qPCR and Western blot (WB) were adopted to detect the molecular mechanisms related to the anti-apoptosis and ROS scavenging effects of gastrodin. RESULTS Our results indicated an obvious protective effect of gastrodin on vascular dementia induced brain ischemia. Administration of gastrodin could improve the impaired learning and memory function induced by 2VO procedure in rats. The levels of MDA were partially decreased by the administration of gastrodin. The levels of glutathione peroxidase and total thiol were partially restored by the administration of gastrodin. Cell viability was improved by gastrodin in a dose-dependent pattern on SH-SY5Y cells induced by hydrogen peroxide (P < 0.05). Cell apoptosis rate was reduced by gastrodin in a dose-dependent pattern on SH-SY5Y cells induced by hydrogen peroxide (P < 0.05). Gastrodin could scavenge ROS generation induced by pre-treatment of hydrogen peroxide. Both qPCR and WB results showed significant enhancements on the expression levels of NFE2L2, ADH7, GPX2 and GPX3 (P < 0.05). CONCLUSION Gastrodin administration is protective on the learning and memory functions that might be affected by vascular dementia induced oxidative stress due to brain ischemia. On the molecular level, NFE2L2, ADH7, GPX2 and GPX3 were up regulated by gastrodin.
Fibrillar Amyloid Protein Present in Atheroma Activates CD36 Signal Transduction*

The self-association of proteins to form amyloid fibrils has been implicated in the pathogenesis of a number of diseases including Alzheimer's, Parkinson's, and Creutzfeldt-Jakob diseases. We recently reported that the myeloid scavenger receptor CD36 initiates a signaling cascade upon binding to fibrillar β-amyloid that stimulates recruitment of microglia in the brain and production of inflammatory mediators. This receptor plays a key role in the pathogenesis of atherosclerosis, prompting us to evaluate whether fibrillar proteins were present in atherosclerotic lesions that could initiate signaling via CD36. We show that apolipoprotein C-II, a component of very low and high density lipoproteins, readily forms amyloid fibrils that initiate macrophage inflammatory responses including reactive oxygen production and tumor necrosis factor α expression. Using macrophages derived from wild type and Cd36-/- mice to distinguish CD36-specific events, we show that fibrillar apolipoprotein C-II activates a signaling cascade downstream of this receptor that includes Lyn and p44/42 MAPKs. Interruption of this signaling pathway through targeted deletion of Cd36 or blocking of p44/42 MAPK activation inhibits macrophage tumor necrosis factor α gene expression. Finally, we demonstrate that apolipoprotein C-II in human atheroma co-localizes to regions positive for markers of amyloid and macrophage accumulation. Together, these data characterize a CD36-dependent signaling cascade initiated by fibrillar amyloid species that may promote atherogenesis.
Localized and Delocalized Features of Microscopic Work Functions

Recent measurements of the microscopic work function distributions based on the local tunneling barrier height by means of scanning tunneling microscopy have been reviewed. Highly localized and widely delocalized features of the microscopic work function have been observed. As a former case, individual atoms on NiAl(HO) show element-specific local work functions. On the other hand, the effect of work function reduction by Cs adsorption on Pt(111) extends over an area wider than tens of nanometers. These results indicate that the work function distribution can not be explained within the framework of electric dipole moments induced by surface atoms, and that detailed features of wave functions should be taken into account