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Fragmentation of forest habitat has negative effects on arboreal mammals, compromising their natural dispersal and foraging movements. This paper describes an evolving series of mitigation measures aimed at creating cost-effective continuity pathways for arboreal mammals in Japan. The projects have focused on the endemic Japanese dormouse (Glirulus japonicus) a scarce, but popular and iconic species which provides an effective vehicle for environmental education and public engagement.

Mindfulness-based interventions have been receiving growing attention in cancer care.The purpose of this randomized controlled trial is to examine the effectiveness of mindfulness-based cognitive therapy (MBCT) for psychological distress (anxiety and depression), fear of cancer recurrence (FCR), fatigue, spiritual well-being, and quality of life (QOL) in Japanese ambulatory patients with Stage I-III breast cancer.A total of 74 patients were randomly assigned to either an eight-week MBCT intervention group (n = 38) or a wait-list control group (n = 36). The primary outcome was psychological distress, measured on Hospital Anxiety and Depression Scale. The secondary outcomes were FCR (Concerns About Recurrence Scale-overall anxiety subscale), fatigue (Brief Fatigue Inventory), spiritual well-being (Functional Assessment of Chronic Illness Therapy-Spiritual), QOL (Functional Assessment of Cancer Therapy-General), and mindfulness skills (Five Facet Mindfulness Questionnaire). The participants were assessed at baseline (T0), Week 8 (T1), and Week 12 (T2). The results were analyzed using a intention-to-treat linear mixed model.The participants in the MBCT group experienced significantly better outcomes in their psychological distress (Cohen's d = 1.17; P 0.001), FCR (d = 0.43; P 0.05), fatigue (d = 0.66; P 0.01), spiritual well-being (d = 0.98; P 0.001), and QOL (d = 0.79; P 0.001) compared with the control group. The difference remained significant at T2 (four weeks after completion of the intervention).MBCT was demonstrated to improve well-being that encompasses psychological, physical, and spiritual domains in Japanese patients with nonmetastatic breast cancer. The favorable effect was maintained up to four weeks after the completion of the intervention.

This datasheet on Callosciurus erythraeus covers Identity, Overview, Distribution, Dispersal, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

The role of erythrocytes in platelet adhesion to von Willebrand factor (VWF) on the vessel wall through their membrane glycoprotein (GP)Ibα under blood flow conditions has not yet been elucidated. Blood specimens containing fluorescent-labeled platelets and native, biochemically fixed, or artificial erythrocytes at various hematocrits were perfused on the surface of VWF immobilized on the wall at a shear rate of 1,500 s−1. The rates of platelet adhesion were measured under each condition. The computer simulation of platelet adhesion to the VWF on the wall at the same shear rate was conducted by solving the governing equations with a finite-difference method on a K computer. The rates of platelet adhesion were calculated at various hematocrit conditions in the computational domain of 100 µm (x-axis) × 400 µm (y-axis) × 100 µm (z-axis). Biological experiments demonstrated a positive correlation between the rates of platelet adhesion and hematocrit values in native, fixed, and artificial erythrocytes. (r = 0.992, 0.934, and 0.825 respectively, p

Entecavir (ETV) is a widely used anti-hepatitis B virus (HBV) drug. However, the emergence of resistant mutations in HBV reverse transcriptase (RT) results in treatment failure. To understand the mechanism underlying the development of ETV resistance by HBV RT, we analyzed the L180M, M204V, and L180M/M204V mutants using a combination of biochemical and structural techniques. ETV-triphosphate (ETV-TP) exhibited competitive inhibition with dGTP in both wild-type (wt) RT and M204V RT, as observed using Lineweaver-Burk plots. In contrast, RT L180M or L180M/M204V did not fit either competitive, uncompetitive, noncompetitive, or typical mixed inhibition, although ETV-TP was a competitive inhibitor of dGTP. Crystallography of HIV RT(Y115F/F116Y/Q151M/F160M/M184V), mimicking HBV RT L180M/M204V, showed that the F115 bulge (F88 in HBV RT) caused by the F160M mutation induced deviated binding of dCTP from its normal tight binding position. Modeling of ETV-TP on the deviated dCTP indicated that a steric clash could occur between ETV-TP methylene and the 3′-end nucleoside ribose. ETV-TP is likely to interact primarily with HBV RT M171 prior to final accommodation at the deoxynucleoside triphosphate (dNTP) binding site (Y. Yasutake, S. Hattori, H. Hayashi, K. Matsuda, et al., Sci Rep 8:1624, 2018, https://doi.org/10.1038/s41598-018-19602-9). Therefore, in HBV RT L180M/M204V, ETV-TP may be stuck at M171, a residue that is conserved in almost all HBV isolates, leading to the strange inhibition pattern observed in the kinetic analysis. Collectively, our results provide novel insights into the mechanism of ETV resistance of HBV RT caused by L180M and M204V mutations. IMPORTANCE HBV infects 257 million people in the world, who suffer from elevated risks of liver cirrhosis and cancer. ETV is one of the most potent anti-HBV drugs, and ETV resistance mutations in HBV RT have been extensively studied. Nevertheless, the mechanisms underlying ETV resistance have remained elusive. We propose an attractive hypothesis to explain ETV resistance and effectiveness using a combination of kinetic and structural analyses. ETV is likely to have an additional interaction site, M171, beside the dNTP pocket of HBV RT; this finding indicates that nucleos(t)ide analogues (NAs) recognizing multiple interaction sites within RT may effectively inhibit the enzyme. Modification of ETV may render it more effective and enable the rational design of efficient NA inhibitors.

Nucleoside analogue reverse transcriptase (RT) inhibitors (NRTIs) are major antiviral agents against hepatitis B virus (HBV) and human immunodeficiency virus type-1 (HIV-1). However, the notorious insoluble property of HBV RT has prevented atomic-resolution structural studies and rational anti-HBV drug design. Here, we created HIV-1 RT mutants containing HBV-mimicking sextuple or septuple amino acid substitutions at the nucleoside-binding site (N-site) and verified that these mutants retained the RT activity. The most active RT mutant, HIV-1 RT7MC, carrying Q151M/G112S/D113A/Y115F/F116Y/F160L/I159L was successfully crystallized, and its three-dimensional structure was determined in complex with DNA:dGTP/entecavir-triphosphate (ETV-TP), a potent anti-HBV guanosine analogue RT inhibitor, at a resolution of 2.43 A and 2.60 A, respectively. The structures reveal significant positional rearrangements of the amino acid side-chains at the N-site, elucidating the mechanism underlying the differential susceptibility of HIV-1 and HBV against recently reported 4ʹ-modified NRTIs.

Previously, we proposed the following mechanism for konjac ceramide (kCer)-mediated neurite outgrowth inhibition: kCer binds to Nrp as a Sema3A agonist, resulting in Nrp1/PlexA complex formation and activation of the Sema3A signaling pathway to induce phosphorylation of CRMP2 and microtubule depolymerization. The Sema3A/Nrp1 signaling pathway is known to be also expressed in normal human keratinocytes. To determine whether kCer can function in human keratinocytes as it does in neurites, that is, if it can bind to Nrp1 in place of Sema3A, we studied the effect of kCer on HaCaT cell migration activity. Using a trans-well chamber assay, we compared the effects of Sema3A and kCer on serum-derived cell migration activity. kCer showed Sema3A-like suppression of cell migration activity and induction of cellular Cofilin phosphorylation. In addition, kCer and Sema3A inhibited histamine (His)-enhanced migration of immature HaCaT cells. We have demonstrated that kCer does not interact with histaime receptors H1R or H4R directly, but we speculate that kCer may transduce a signal downstream of the His signaling pathway., Highlights • Konjac ceramide (kCer) inhibits HaCaT cell migration by Sema3A-like action. • kCer displaces the binding of Sema3A to cell surface receptor. • kCer inhibits histamine-induced stimulation of HaCaT cell migration. • kCer does not interact with histamine receptors, H1R and H4R.

This retrospective study evaluated the results of Gamma Knife surgery (GKS) for symptomatic cavernous malformations (CM) of the brain.From 1993 till 2014, 11 patients (mean age 44 years) with a symptomatic CM underwent GKS at Tokyo Women's Medical University. In six cases, the disease manifested with hemorrhaging. Seizures and a neurological deficit were noted in four patients each. The CM were located in the brainstem (in 5 cases), basal ganglia (in 2 cases), thalamus (in 2 cases), and cerebral lobe (in 2 cases). The mean lesion volume was 1.46 cc. The mean marginal dose was 15.3 Gy. The mean length of follow-up after GKS was 78.5 months.At the last follow-up, the general status was considered excellent, fair, and poor in 8 patients (73%), 1 patient (9%), and 2 patients (18%), respectively. The annual hemorrhage rates per case-year were 2.94% from birth till GKS, 20.20% from the first hemorrhage till GKS, 4.54% within the first 2 years after GKS, and 1.39% within the entire follow-up period after GKS. Two patients attained seizure-free status after treatment.GKS may be considered as a possible management option for symptomatic CM, since it reduces the subsequent hemorrhage risk after the initial bleeding episode. Moreover, in some patients, cessation of symptomatic epilepsy after treatment may be expected.

Total surgical removal of a pituitary adenoma (PA) invading the cavernous sinus (CS) is challenging and carries a significant risk of postoperative complications. As an alternative treatment strategy, after incomplete resection, such tumors may undergo stereotactic radiosurgery-in particular, Gamma Knife surgery (GKS). Treatment planning based on advanced neuroimaging (e.g., thin-slice 3-dimensional postcontrast constructive interference in steady state (CISS) images) allows clear visualization of the target microanatomy, which results in highly conformal and selective radiation delivery to the lesion with preservation of adjacent functionally important neurovascular structures. In the Tokyo Women's Medical University experience of GKS for 43 nonfunctioning and 46 hormone-secreting PA invading the CS, with a minimum follow-up period of 5 years (mean 76 months, range 60-118 months), the tumor control rate has reached 97%, and a significant volume reduction (≥50%) has been seen in 24% of lesions. In cases of hormone-secreting neoplasms, normalization (in 18 patients; 39%) or improvement (in 22 patients; 48%) of endocrinological function has been noted. Importantly, such effects have been sufficiently durable. Complications have been extremely rare and limited to transient cranial nerve palsy (in 2% of cases). Notably, no patient in our series has had a new pituitary hormone deficit after irradiation. Thus, subtotal resection followed by GKS may be considered a valuable alternative to aggressive surgery for a PA invading the CS.

ObjectivesTo deliver mindfulness-based cognitive therapy (MBCT) efficiently, the present study aimed (1) to identify predictors and moderators of patients who benefit from MBCT for psychological distress and (2) to explore the initial treatment reaction to identify the optimal number of sessions that produce a significant clinical effect.MethodsThis is the secondary analysis of a randomized controlled trial of MBCT for breast cancer patients (N = 74). We classified the participants into remitters vs. non-remitters, and responder vs. non-responders, according to the total score of the Hospital Anxiety and Depression Scale at the end of the intervention. We conducted multivariate analyses to explore for predictors of response and remission. We adopted generalized estimating equations to explore the optimal number of sessions.ResultsSociodemographic and clinical backgrounds did not have significant influence on the treatment outcomes of the MBCT. Better program adherence, which was represented as the participants’ better attendance to the MBCT program, was a significant predictor of both remission and response [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.25–2.89, p = 0.003, and OR = 1.72, 95% CI 1.12–2.65, p = 0.013, respectively]. It was not until seventh session that the remission rate exceeded 50% and the response rate showed significance.Significance of resultsSociodemographic and clinical characteristics did not significantly influence the treatment outcomes, while homework minutes and class attendance had significant effects on treatment outcomes. This implies that MBCT is recommended to any cancer patient, if he/she is motivated to the program, regardless of their sociodemographic and clinical characteristics. Patients are encouraged to attend a standard MBCT program (eight sessions) and do the assigned homework as intensely as possible. Further studies with larger sample and objective measurements are desired.

BACKGROUND Gamma Knife radiosurgery (GKRS) is a safe and effective treatment, but it has a risk of bleeding. Herein, the authors describe their experience with some patients who required surgical removal of cerebral arteriovenous malformations (AVMs) located mainly in eloquent areas of the brain after GKRS, and they consider the advantages of surgical removal after GKRS. OBSERVATIONS Twelve patients who had undergone surgical removal of AVMs after GKRS at Tokyo Women’s Medical University between April 2013 and July 2019 were selected for analysis. All participants underwent GKRS as first-line therapy for AVMs located in an eloquent region or if requested by the patient. Complete obliteration was achieved in 7 patients, and the size of the nidus decreased in 3 patients during the follow-up period. The Spetzler-Martin grade decreased in 11 patients. Three patients experienced symptomatic intracerebral hemorrhage before and after confirmation of complete obliteration of the nidus via GKRS, and 7 patients experienced some neurological deficits because of an encapsulated expanding hematoma. All patients underwent resection of the nidus without complications. The preoperative neurological deficits improved in 6 patients and remained unchanged in 6 patients. LESSONS This report indicates that performing GKRS before surgery may be useful for future multimodal therapy.

Quercus acorns and coniferous cones are the main food sources for tree squirrels, and the chemical contents of seeds, such as tannins and terpenes, are predicted to affect the squirrels' food preference. The tolerance of squirrels to chemical contents may vary between species that have evolved in different environments. The consumption of artificial food containing tannic acids or terpenes were compared between the endemic Sciurus lis and two alien species, S. vulgaris and Callosciurus erythraeus. Sciurus lis ate foods containing up to 4% tannic acid, whereas S. vulgaris and C. erythraeus ate foods containing 8% tannic acid. Sciurus lis and S. vulgaris could eat food containing a high concentration of terpenes (up to 0.3% α-pinene and 2% limonene), whereas the food consumption by C. erythraeus decreased drastically with increasing terpene concentrations. The two alien squirrels are highly resistant to tannins and thus the acorns of most Quercus species may be available for them. Sciurus lis exhibits a lower tolerance to tannins, but can consume foods with high concentrations of terpenes, suggesting a strong adaptation to coniferous forests, but not to Quercus forests. More attention must be paid to conserving suitable habitats for S. lis, an endemic relict species.

Acoustic signals are one of the reproductive isolation mechanisms that can be a driving force for speciation. Evidence that geographic variation in mating calls can cause reproductive isolation is abundant for birds and frogs, but not for mammals. In the Callosciurus genus of tree squirrels distributed in Southeast Asia, males emit mating calls to attract females and the sound properties are known to be distinctly different among coexisting congeneric species. We investigated whether mating calls emitted by males differ between ten populations of the widely distributed C. erythraeus/C. finlaysonii complex. Based on the acoustic properties, the populations were divided into four groups (South Vietnam, Taiwan, eastern China, and western areas including Thailand and western China), which resulted in a high discrimination rate of 94.7% by a discriminant function analysis. A playback experiment was also conducted to determine whether the mating calls from different localities were as effective in attracting conspecific individuals as those in the same locality. In Kanagawa, Japan, where squirrels were introduced from Taiwan in the 1950s, squirrels responded more frequently to the playback sounds recorded in Taiwan compared to those recorded in Thailand. In addition, the response of squirrels decreased with an increase in the difference in acoustic characteristics compared to that from the original habitat. These results suggest that local differences in acoustic characteristics could be one of the mechanisms that promote reproductive isolation of geographically distant populations of Callosciurus. Acoustic signals are one of the reproductive isolation mechanisms that can be a driving force for speciation. The tree squirrel genus Callosciurus (Sciuridae) is widely distributed in Southeast Asia and is one of the few suitable mammals for testing the premating isolation mechanism using acoustic signals. The mating calls of the C. erythraeus/C. finlaysonii complex were divided into four geographical groups (Taiwan, Vietnam, eastern China, and Thailand) by a discriminant function analysis. Playback experiments revealed that the squirrels responded more frequently to the sounds of their own group compared to those of other groups. In addition, the response of the squirrels decreased with an increase in the difference in acoustic characteristics compared to that from the original habitat. Local differences in acoustic characteristics could be one of the mechanisms that promote reproductive isolation of geographically distant populations of Callosciurus.

Total surgical removal of a pituitary adenoma (PA) invading the cavernous sinus (CS) is challenging and carries a significant risk of postoperative complications. As an alternative treatment strategy, after incomplete resection, such tumors may undergo stereotactic radiosurgery—in particular, Gamma Knife surgery (GKS). Treatment planning based on advanced neuroimaging (e.g., thin-slice 3-dimensional postcontrast constructive interference in steady state (CISS) images) allows clear visualization of the target microanatomy, which results in highly conformal and selective radiation delivery to the lesion with preservation of adjacent functionally important neurovascular structures. In the Tokyo Women’s Medical University experience of GKS for 43 nonfunctioning and 46 hormone-secreting PA invading the CS, with a minimum follow-up period of 5 years (mean 76 months, range 60–118 months), the tumor control rate has reached 97%, and a significant volume reduction (≥50%) has been seen in 24% of lesions. In cases of hormone-secreting neoplasms, normalization (in 18 patients; 39%) or improvement (in 22 patients; 48%) of endocrinological function has been noted. Importantly, such effects have been sufficiently durable. Complications have been extremely rare and limited to transient cranial nerve palsy (in 2% of cases). Notably, no patient in our series has had a new pituitary hormone deficit after irradiation. Thus, subtotal resection followed by GKS may be considered a valuable alternative to aggressive surgery for a PA invading the CS.

Objective: This retrospective study evaluated the results of Gamma Knife surgery (GKS) for symptomatic cavernous malformations (CM) of the brain.

Aim. To predict platelet accumulation around stent struts in the presence or absence of tissue defects around them. Methods. Computer simulations were performed using virtual platelets implementing the function of the three membrane proteins: glycoprotein (GP) Ibα, GPIIb/IIIa, and GPVI. These platelets were perfused around the stent struts implanted into the vessel wall in the presence or absence of tissue defects around them using within the simulation platform. The number of platelets that adhered around stent struts was calculated by solving the blood flow using Navier–Stokes equation along with the adhesion of membrane protein modeled within the platform. Results. Platelet accumulation around stent struts occurred mostly at the downstream region of the stent strut array. The majority of platelets adhered at the downstream of the first bend regardless of the tissue defect status. Platelet adhesion around stent struts occurred more rapidly in the presence of tissue defects. Conclusion. Computer simulation using virtual platelets suggested a higher rate of platelet adhesion in the presence of tissue defects around stent struts.

Konjac ceramide (kCer) is a plant-type ceramide composed of various long-chain bases and a-hydroxyl fatty acids. The presence of d4t,8t-sphingadienine is essential for semaphorin 3A (Sema3A)-like activity. Herein, we examined the three neuropilin 1 (Nrp1) domains (a1a2, b1b2, or c), and found that a1a2 binds to d4t,8t-kCer and possesses Sema3A-like activity. kCer binds to Nrp1 with a weak affinity of mM dissociation constant (Kd). We wondered whether bovine serum albumin could influence the ligand&ndash, receptor interaction that a1a2 has with a single high affinity binding site for kCer (Kd in nM range). In the present study we demonstrated the influence of bovine serum albumin. Thermal denaturation indicates that the a1a2 domain may include intrinsically disordered region (IDR)-like flexibility. A potential interaction site on the a1 module was explored by molecular docking, which revealed a possible Nrp1 activation mechanism, in which kCer binds to Site A close to the Sema3A-binding region of the a1a2 domain. The a1 module then accesses a2 as the IDR-like flexibility becomes ordered via kCer-induced protein rigidity of a1a2. This induces intramolecular interaction between a1 and a2 through a slight change in protein secondary structure.

Vocal communication plays an important role in the mating behaviour of arboreal squirrels. Callosciurus is a genus of tree squirrels that includes 15 species distributed in Southeast Asia, and congeneric species often inhabit the same forest. As closely related species of Callosciurus have the potential to interbreed, species recognition from mating calls may be a fundamental reproductive barrier. We compared seven acoustic characteristics of male mating calls in six Callosciurus species and estimated whether the species differences were clear enough to function as a cue. Discriminant function analyses (DFA) classified 87.4% of mating calls to the correct species. All of the calls by C notatus, C. nigrovittatus and C. caniceps, and 88% of the calls by C. prevostii, were assigned to the correct species, while the percentage of correct classifications was lower in C. finlaysonii (71%) and C. erythraeus (63%). We compared these results with the genetic relationships to determine whether interspecific acoustic differences are caused by adaptive selection (habitat selection and body size) or by a stochastic process (drift). The genetic relationships among the six species were coincident with the differences in mating calls, which supports the stochastic divergence. Species-specific mating calls may be a useful cue for species recognition in Callosciurus, and thus these calls could be an effective trait for phylogenetic analysis in Callosciurus.

Aims Detection of early-stage atherosclerosis in type 2 diabetes mellitus (T2DM) patients is important for preventing cardiovascular disease. A phased tracking method for evaluating arterial wall elasticity sensitively detects early-stage atherosclerosis. However, biochemical markers for early-stage atherosclerosis have yet to be established. Methods This cross-sectional study enrolled 180 T2DM patients, who were classified as not having atherosclerosis according to the carotid intima-media thickness (IMT) criteria. We measured serum cystatin C, the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), and analyzed the associations between these markers and arterial wall elasticity (Eθ), IMT and the cardio-ankle velocity index. Results Multiple linear regression analyses revealed that cystatin C was significantly associated with Eθ, while neither eGFR nor ACR showed an association. Furthermore, among the examined atherosclerotic markers, Eθ was most reliably associated with cystatin C. Additionally, the association between cystatin C and Eθ disappeared in the low elasticity subgroup, which included subjects in whom no atherosclerotic changes had yet been initiated. Conclusions In T2DM patients without apparent arterial wall thickening, cystatin C is strongly and independently associated with arterial wall elasticity, which reflects the degree of subclinical atherosclerosis. Thus, cystatin C is a potentially useful marker of early-stage atherosclerosis.

The tuber of the konjac plant is a source enriched with GlcCer (kGlcCer), and has been used as a dietary supplement to improve the dry skin and itching that are caused by a deficiency of epidermal ceramide. Previously, we showed chemoenzymatically prepared konjac ceramide has a neurite-outgrowth inhibitory effect that is very similar to that of Sema3A and is not seen with animal-type ceramides. While, it has been unclear whether kCer may act on Sema3A or TrkA signaling pathway. In the present study, we showed kCer induces phosphorylation of CRMP2 and microtubules depolymerization via Sema3A signaling pathway not TrkA. It is concluded that kCer may be a potential Sema3A-like agonist that activates Sema3A signaling pathway directly.

Konjac ceramide (kCer) can be prepared by a chemoenzymatic method as previously published (Usuki, S.; Tamura, N.; Sakai, S.; Tamura, T.; Mukai, K.; Igarashi, Y. Biochem. Biophys. Rep. 5, 160-167 (2016)). Thus prepared kCer showed an activation effect on Sema3A signaling pathway to induce phosphorylation of CRMP2 and microtubule depolymerizaion, resulting in opposing NGF-induced neurite outgrowth. In the present study, we have shown that kCer is a potential Sema3A-like ligand that has a competitive effect on Sema3A binding to a cell surface receptor Nrp1, but animal-type ceramides have no effect on Sema3A binding to Nrp1. In addition, kCer showed a direct molecular interaction with Nrp1, but animal-type ceramides, C16Cer, C18Cer, and C24Cer show no specific bindings to Nrp1. Further, kCer showed an additive effect to activate the Sema3A signaling pathway together with low-dose Sema3A but a reversed effect to inhibit this pathway when combined with high-dose Sema3A.

Finlayson’s squirrel, Callosciurus finlaysonii, is distributed in lowland forests throughout South-East Asia. Its pelage colour is conspicuous and polymorphic (red, black, white and a mixture of these colours), which is characteristic of the species, with 16 subspecies described based on pelage colour patterns. Two closely related species, the brown C. erythraeus and the orange C. caniceps, are also distributed throughout the region. To examine whether the conspicuous pelage colour is a visual clue for species/subspecies discrimination, we experimentally assessed the colour vision of C. finlaysonii. Optically measured pelage colours of the dorsal body differed greatly among seven subspecies of C. finlaysonii and also differed among the three species of the region. Colour vision tests revealed that C. finlaysonii can discriminate the colour of conspecific white, black, and red pelages from the orange pelages of C. caniceps. They can also discriminate the brown pelages of C. erythraeus and conspecific white...

Finlayson’s squirrel (Callosciurus finlaysonii) is distributed in lowland forests in Southeast Asia. The pelage colour is conspicuously polymorphic, and 16 subspecies have been described based on pelage colour pat-terns. Among them, 12 subspecies are distributed in Thailand, of which 7 are on the mainland and 5 are on islands. In addition, the distribution range of another closely related species, Pallas’s squirrel (Callosciurus erythraeus), overlaps the range of C. finlaysonii in western Thailand. In this study, phyloge-netic analysis based on mitochondrial DNA suggested that C. finlaysonii and C. erythraeus did not form separate monophyletic groups. This C. finlaysonii/C erythraeus complex in Thailand consisted of seven divergent groups, some of which may have arisen from isolation due to large rivers and seas: (1) C. f. nox/cinnamomeus, (2) C f. finlaysonii/folletti/trotteri, (3) C.f. menamicus, (4) C. erythraeus, (5) C.f. annella-tus, (6) C.f. bocourti/boonsongi/floweri, and (7) C f. frandseni/albivexilli. Pelage colour did not consistently correspond to these genetic groups, suggesting that specific colours may have been acquired multiple times or the genes associated with colour may have variations and polymorphisms within subspecies. Several small populations in the lowlands and on small islands had lower genetic diversity. To conserve the local genetic diversity of C. finlaysonii, it may be necessary to enact legal restrictions on their trade and hunting.

Chronic hepatitis B virus (HBV) infection is a major public health problem that affects millions of people worldwide. Nucleoside analogue reverse transcriptase (RT) inhibitors, such as entecavir (ETV) and lamivudine (3TC), serve as crucial anti-HBV drugs. However, structural studies of HBV RT have been hampered due to its unexpectedly poor solubility. Here, we show that human immunodeficiency virus type-1 (HIV-1) with HBV-associated amino acid substitutions Y115F/F116Y/Q151M in its RT (HIVY115F/F116Y/Q151M) is highly susceptible to ETV and 3TC. Additionally, we experimentally simulated previously reported ETV/3TC resistance for HBV using HIVY115F/F116Y/Q151M with F160M/M184V (L180M/M204V in HBV RT) substituted. We determined crystal structures for HIV-1 RTY115F/F116Y/Q151M:DNA complexed with 3TC-triphosphate (3TC-TP)/ETV-triphosphate (ETV-TP)/dCTP/dGTP. These structures revealed an atypically tight binding conformation of 3TC-TP, where the Met184 side-chain is pushed away by the oxathiolane of 3TC-TP and exocyclic methylene of ETV-TP. Structural analysis of RTY115F/F116Y/Q151M/F160M/M184V:DNA:3TC-TP also demonstrated that the loosely bound 3TC-TP is misaligned at the active site to prevent a steric clash with the side chain γ-methyl of Val184. These findings shed light on the common structural mechanism of HBV and HIV-1 resistance to 3TC and ETV and should aid in the design of new agents to overcome drug resistance to 3TC and ETV.

Objective To analyze why women quit full-time employment as neurosurgeons and to discuss the conditions required for their reinstatement. Methods We asked 94 core hospitals providing training programs in the board certification system adopted by the Japan Neurosurgical Society to indicate the total number and present status of women in their department and to send our anonymous questionnaire to women who had formerly worked as full-time neurosurgeons. The questionnaire consisted of closed and open questions on their reasons for quitting as full-time neurosurgeons. Results Among 427 women evaluated, 72 (17%) had quit full-time employment as neurosurgeons. Twenty-one women who had quit 3–21 years after starting their neurosurgery careers responded to the questionnaire, including 17 board-certified neurosurgeons, 11 individuals with master's degrees, and 16 mothers. Their main reasons for quitting full-time work were difficulty in balancing their neurosurgical career and motherhood (52%) and the physical burden (38%). At the time of quitting, only 2 units (5%) had a career counseling system for women. Two thirds of participants might resume full-time work as neurosurgeons in the future. Their support system during pregnancy and the child-raising period, and understanding of male bosses and colleagues were identified as the key themes. Conclusions The Japan Neurosurgical Society could facilitate supportive environments for women in neurosurgery by enhancing adequate childcare services, changing the work style of full-time neurosurgeons to incorporate diverse working styles, shorter working hours, understanding of their bosses and colleagues, and a career counseling system.

In Japan, Clinical Practice Guidelines are defined as a document that presents appropriate recommendations to assist patients and practitioners in making decisions regarding clinical practice of marked importance, based on the body of evidence evaluated and integrated by systematic reviews and the balance between benefits and harm outlined by the Medical Information Network Distribution Services (Minds). Their successful implementation should improve the quality of care by decreasing inappropriate variation and expediting the application of effective advances to everyday practice. The process of developing CPGs includes dissemination, implementation, and assessment after publication. Some of the countries or guideline developers conducted research on factors of facilitators and barriers influencing the imple- mentation of CPGs. In Japanese mental health, little is known about the influence of CPGs. To gain an understanding of the current status of CPGs for mental health, we collected all published CPGs using the following databases: Minds website, Toho University and ICHUSHI Clinical Practice Guidelines Database, and J-GLOBAL. As a result, we found 1,117 articles. Because of the overlap among the 3 databases, trans- lated versions of foreign CPGs, commentaries, and review articles, 78 CPGs were extracted. We categorized the 78 CPGs into the following types : disease, writers, publication year, method of development, publication type, and revised or not. Through this survey, we found that there are many CPGs, they are difficult to identify, and their implementation and dissemination rates are unclear. CPGs are one type of medical information, and their use causes some challenges. When we develop CPGs, we have to per- form a systematic review of the evidence. It is known that there is a gap between evidence and practice in healthcare research. Also, multimorbidity is now very common. CPGs are gen- erally developed for a single disease, and so the application of CPGs is difficult when a patient has more than one disease. Although CPGs for mental health are being developed in Japan, there have been few studies on the influence, barriers, and facilitators of dissemination and implementation. Further research is needed on how to utiliz medical information effectively in order to improve the quality of health care.