Accounting for geographic variation in species-habitat associations during habitat suitability modeling.

Range-wide species conservation efforts are facilitated by spatially explicit estimates of habitat suitability. However, species-environment relationships often vary geographically and models assuming geographically constant relationships may result in misleading inferences. We present the first range-wide habitat suitability model (HSM) for the federally threatened eastern indigo snake (Drymarchon couperi) as a case study illustrating an approach to account for known latitudinal variation in habitat associations. Specifically, we modeled habitat suitability using interactive relationships between minimum winter temperature and several a priori environmental covariates and compared our results to those from models assuming geographically constant relationships. We found that multi-scale models including interactive effects with winter temperature outperformed single-scale models and models not including interactive effects with winter temperature. Our top-ranked model had suitable range-wide predictive performance and identified numerous large (i.e., ≥1000 ha) potential habitat patches throughout the indigo snake range. Predictive performance was greatest in southern Georgia and northern Florida likely reflecting more restrictive indigo snake habitat associations in these regions. This study illustrates how modeling interactive effects between temperature and environmental covariates can improve the performance of HSMs across geographically varying environmental gradients.

Evaluation of the COVID-19 pandemic effect on the development of somatic symptoms in patients with mood disorders: a case-control study.

Somatic symptoms are one of the most common complaints among patients with psychiatric disorders and are considered as one of the most common psychiatric disorders in the new coronavirus pandemic. This study aimed to evaluate the effect of the COVID-19 pandemic on the physical symptoms in patients with mood disorders and compare it with healthy individuals. In this case-control study, 67 patients with mood disorders were referred to the psychiatric clinic of 5 Azar Hospital in Gorgan, who met the inclusion criteria, and 68 healthy individuals as control group were entered into the study. For all participants after informed consent, a demographic information questionnaire was completed along with Screening for Somatic Symptoms-7 (SOMS7) and Patient Health Questionnaire-15 (PHQ-15), and the data were analysed by SPSS software version 25. The mean score obtained for the SOMS-7 questionnaire for the group of patients with mood disorders and the control group was 32.37 ± 8.19 and 35.42 ± 11.3, respectively. The mean obtained for the PHQ-15 questionnaire for the mood disorders group and the control group was 8.56 ± 5.93 and 5.86 ± 4.63, respectively. In the mood disorder group, 26.9% of patients had no risk for physical symptoms, 31.3% of patients had a low risk, 25.4% of patients had a moderate risk, and 16.4% of patients had a high risk for physical symptoms. The statistical test showed that although the risk of physical symptoms was high in both groups, this rate was higher in the group with mood disorders, and there is a significant difference between the two groups (P < 0.05). The results also showed a significant and direct relationship between the two questionnaires (P < 0.05). According to the results, although the prevalence of somatic symptoms increased in both groups, the prevalence of somatic symptoms is significantly higher in the mood disorder group.

Multiscale assessment of functional connectivity: Landscape genetics of eastern indigo snakes in an anthropogenically fragmented landscape in central Florida.

Landscape features can strongly influence gene flow and the strength and direction of these effects may vary across spatial scales. However, few studies have evaluated methodological approaches for selecting spatial scales in landscape genetics analyses, in part because of computational challenges associated with optimizing landscape resistance surfaces (LRS). We used the federally threatened eastern indigo snake (Drymarchon couperi) in central Florida as a case study with which to compare the importance of landscape features and their scales of effect in influencing gene flow. We used genetic algorithms (ResistanceGA) to empirically optimize LRS using categorical land cover surfaces, multiscale resource selection surfaces (RSS), and four combinations of landscape covariates measured at multiple spatial scales (multisurface multiscale LRS). We compared LRS where scale was selected using pseudo- and full optimization. Multisurface multiscale LRS received more empirical support than LRS optimized from categorical land cover surfaces or RSS. Multiscale LRS with scale selected using full optimization generally outperformed those with scale selected using pseudo-optimization. Multiscale LRS with large spatial scales (1200-1800 m) received the most empirical support. Our results highlight the importance of considering landscape features across multiple spatial scales in landscape genetic analyses, particularly broad scales relative to species movement potential. Different effects of scale on home range-level movements and dispersal could explain weak associations between habitat suitability and gene flow in other studies. Our results also demonstrate the importance of large tracts of undeveloped upland habitat with heterogenous vegetation communities and low urbanization for promoting indigo snake connectivity.

Relationships of catch-per-unit-effort metrics with abundance vary depending on sampling method and population trajectory.

Catch-per-unit-effort (CPUE) is often used to monitor wildlife populations and to develop statistical population models. Animals caught and released are often not included in CPUE metrics and their inclusion may create more accurate indices of abundance. We used 21 years of detailed harvest records for bobcat (Lynx rufus) in Wisconsin, U.S.A., to calculate CPUE and 'actual CPUE' (ACPUE; including animals caught and released) from bobcat hunters and trappers. We calibrated these metrics to an independent estimate of bobcat abundance and attempted to create simple but effective models to estimate CPUE and ACPUE using harvest success data (i.e., bobcats harvested/available permits). CPUE showed virtually no relationship with bobcat abundance across all years, but both CPUE and ACPUE had stronger, non-linear, and negative relationships with abundance during the periods when the population was decreasing. Annual harvest success strongly predicted composite ACPUE and CPUE from hunters and trappers and hunter ACPUE and CPUE but was a poorer predictor of trapper ACPUE and CPUE. The non-linear, and sometimes weak, relationships with bobcat abundance likely reflect the increasing selectivity of bobcat hunters for trophy animals. Studies calibrating per-unit-effort metrics against abundance should account for population trajectories and different harvest methods (e.g., hunting and trapping). Our results also highlight the potential for estimating per-unit-effort metrics from relatively simple and inexpensive data sources and we encourage additional research into the use of per-unit-effort metrics for population estimation.

The Influence of Sex and Season on Conspecific Spatial Overlap in a Large, Actively-Foraging Colubrid Snake.

Understanding the factors influencing the degree of spatial overlap among conspecifics is important for understanding multiple ecological processes. Compared to terrestrial carnivores, relatively little is known about the factors influencing conspecific spatial overlap in snakes, although across snake taxa there appears to be substantial variation in conspecific spatial overlap. In this study, we described conspecific spatial overlap of eastern indigo snakes (Drymarchon couperi) in peninsular Florida and examined how conspecific spatial overlap varied by sex and season (breeding season vs. non-breeding season). We calculated multiple indices of spatial overlap using 6- and 3-month utilization distributions (UD) of dyads of simultaneously adjacent telemetered snakes. We also measured conspecific UD density values at each telemetry fix and modeled the distribution of those values as a function of overlap type, sex, and season using generalized Pareto distributions. Home range overlap between males and females was significantly greater than overlap between individuals of the same sex and male home ranges often completely contained female home ranges. Male home ranges overlapped little during both seasons, whereas females had higher levels of overlap during the non-breeding season. The spatial patterns observed in our study are consistent with those seen in many mammalian carnivores, in which low male-male overlap and high inter-sexual overlap provides males with greater access to females. We encourage additional research on the influence of prey availability on conspecific spatial overlap in snakes as well as the behavioral mechanisms responsible for maintaining the low levels of overlap we observed.

Oct4 transcription factor in conjunction with valproic acid accelerates myelin repair in demyelinated optic chiasm in mice.

Multiple sclerosis is a demyelinating disease with severe neurological symptoms due to blockage of signal conduction in affected axons. Spontaneous remyelination via endogenous progenitors is limited and eventually fails. Recent reports showed that forced expression of some transcription factors within the brain converted somatic cells to neural progenitors and neuroblasts. Here, we report the effect of valproic acid (VPA) along with forced expression of Oct4 transcription factor on lysolecithin (LPC)-induced experimental demyelination. Mice were gavaged with VPA for one week, and then inducible Oct4 expressing lentiviral particles were injected into the lateral ventricle. After one-week induction of Oct4, LPC was injected into the optic chiasm. Functional remyelination was assessed by visual-evoked potential (VEP) recording. Myelination level was studied using FluoroMyelin staining and immunohistofluorescent (IHF) against proteolipid protein (PLP). IHF was also performed to detect Oct4 and SSEA1 as pluripotency markers and Olig2, Sox10, CNPase and PDGFRα as oligodendrocyte lineage markers. One week after injection of Oct4 expressing vector, pluripotency markers SSEA1 and Oct4 were detected in the rims of the 3rd ventricle. LPC injection caused extensive demyelination and significantly delayed the latency of VEP wave. Animals pre-treated with VPA+Oct4 expressing vector, showed faster recovery in the VEP latency and enhanced myelination. Immunostaining against oligodendrocyte lineage markers showed an increased number of Sox10+ and myelinating cells. Moreover, transdifferentiation of some Oct4-transfected cells (GFP+ cells) to Olig2+ and CNPase+ cells was confirmed by immunostaining. One-week administration of VPA followed by one-week forced expression of Oct4 enhanced myelination by converting transduced cells to myelinating oligodendrocytes. This finding seems promising for enhancing myelin repair within the adult brains.

Enhanced remyelination following lysolecithin-induced demyelination in mice under treatment with fingolimod (FTY720).

Multiple sclerosis (MS) is a chronic, progressive demyelinating disorder which affects the central nervous system (CNS) and is recognized as the major cause of nervous system disability in young adults. Enhancing myelin repair by stimulating endogenous progenitors is a main goal in efforts for MS treatment. Fingolimod (FTY720) which is administrated as an oral medicine for relapsing-remitting MS has direct effects on neural cells. In this study, we hypothesized if daily treatment with FTY720 enhances endogenous myelin repair in a model of local demyelination induced by lysolecithin (LPC). We examined the response of inflammatory cells as well as resident OPCs and evaluated the number of newly produced myelinating cells in animals which were under daily treatment with FTY720. FTY720 at doses 0.3 and 1mg/kg decreased the inflammation score at the site of LPC injection and decreased the extent of demyelination. FTY720 especially at the lower dose increased the number of remyelinated axons and newly produced myelinating cells. These data indicate that repetitive treatment with FTY720, behind an anti-inflammatory effect, exerts beneficial effects on the process of endogenous repair of demyelinating insults.

Oligoprogenitor cells derived from spermatogonia stem cells improve remyelination in demyelination model.

Embryonic stem (ES) like cells-derived testis represents a possible alternative to replace of neurons and glia. Here, we differentiated spermatogonia cells to oligoprogenitor (OP) like cells and transplanted them to demyelination model and assess their recovery potential in a demyelinated corpus callosum model in rats. ES like cells were differentiated to OP like cells using appropriate inducers and were transplanted in situ to demyelinated corpus callosum. Cell integration as well as demyelination extension and myelination intensity changes were evaluated using histologic studies and immunocytochemistry after 2 and 4 weeks post transplantation. Investigation of Nestin, NF68, Olig2, and NG2 by immunocytochemical technique indicated the differentiation of ES like cells to neuroprogenitor and oligodendrocyte like cells in each induction stage. Histologic findings showed a significant decrease in demyelination extension and a significant increase in remyelination intensity in cell transplanted groups. Also on the base of PLP expression, differentiation of transplanted cells was confirmed to myelinogenic cells using immunocytochemistry technique. We conclude that ES like cells derived from spermatogonia cells can be differentiated to OP like cells that can form myelin after transplantation into the demyelination model in rat, this represents recovery potential of spermatogonia cells which opens new window for cell therapeutic approaches using spermatogonial stem cells.

Examining the effect of the CaMKII inhibitor administration in the locus coeruleus on the naloxone-precipitated morphine withdrawal signs in rats.

Drug addiction is an occurrence with physiological, psychological, and social outcomes. Repeated drug exposure causes neuronal adaptations and dependency. It has been shown that CaMKIIα enzyme contributes to morphine dependency. The locus coeruleus nucleus has been implied in the morphine withdrawal syndrome. This research focuses on the behavioral and molecular adaptations that occur in the locus coeruleus neurons in response to the chronic morphine exposure. Adult male Wistar rats were injected by morphine sulfate (10 mg/kg/s.c.) at an interval of 12 h for a period of nine subsequent days. On the tenth day, naloxone (1 mg/kg/i.p.) was injected 2 h after the morphine administration. Somatic withdrawal signs were investigated for 30 min. We concluded that the inhibition of CaMKIIα by administration of KN-93, the specific inhibitor of this enzyme, significantly attenuated some of the withdrawal signs. In molecular method, the expression of CaMKIIα protein has been enhanced in locus coeruleus of the morphine dependent rats. These findings indicate that CaMKIIα may be involved in the modulation of the naloxone-induced withdrawal syndrome, and treatment with KN-93 may have some effects on this system.

Insulin resistance and insulin secretion changes in kidney transplant recipients with normal graft function compared with those with delayed graft function early after transplantation.

INTRODUCTION: We compared insulin resistance (IR) and insulin secretion (IS) among kidney transplant recipients with normal versus delayed graft function (DGF) early after transplantation. METHODS: We selected 55 kidney transplant recipients without a history of clinical diabetes mellitus. The basal values of glucose (G) and insulin (I) were used to calculate indices of IR and IS before, on the third day, as well as at the end of the first, second, and third weeks after transplantation. RESULTS: Before transplantation IR was more prevalent (62.5%) than impaired IS (20%; P = .012). Three weeks after engraftment, IR was significantly reduced (P < .001), whereas the reduction in the IS was not significant (P = .17). Splitting the results between normal and delayed functioning grafts showed a significant difference in both IR and IS between the 2 groups on the third day after transplantation (P = .018 and .024, respectively). Regression models showed that only cumulative administered cyclosporine dose and plasma creatinine were significantly (or near significantly) associated with IR (P = .04 and .07, respectively). CONCLUSION: Among patients with DGF there was a significantly greater prevalence of IR and IS compared with successfully engrafted patients in the middle of the first week after transplantation. With resumption of normal kidney function among the DGF group, this difference disappeared at the end of the third week after transplantation.

The role of adenosine A(1) receptors in mediating the inhibitory effects of low frequency stimulation of perforant path on kindling acquisition in rats.

Low frequency stimulation (LFS) has an inhibitory effect on rapid perforant path kindling acquisition. In the present study the role of adenosine A(1) and A(2A) receptors in mediating this inhibitory effect was investigated. Rats were kindled by perforant path stimulation using rapid kindling procedures (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, and 50-150 muA) was applied to the perforant path immediately after termination of each rapid kindling stimulation. 1,3-Dimethyl-8-cyclopenthylxanthine (CPT; 50 muM), a selective A(1) antagonist and ZM241385 (ZM, 200 muM), a selective A(2A) antagonist were daily microinjected into the lateral ventricle 5 min before kindling stimulations. LFS had an inhibitory effect on kindling development. Pretreatment of animals with CPT reduced the inhibitory effect of LFS on kindling rate and suppressed the effects of LFS on potentiation of population EPSP during kindling acquisition. In addition, CPT was able to antagonize the effects of LFS on kindling-induced increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression. ZM pretreatment had no effect on antiepileptogenic effects of LFS in kindling acquisition. In addition, LFS prevented the kindling-induced elevation of cyclic AMP (cAMP) levels in kindled animals. Based on these results, we suggest that the antiepileptogenic effects of LFS on perforant path kindling might be mediated through activation of adenosine A(1), but not A(2A) receptors. Moreover, modulation of cAMP levels by LFS may potentially be an important mechanism which explains the anticonvulsant effects of LFS in kindled seizures.

Stress- and non-stress-mediated mechanisms are involved in pain-induced apoptosis in hippocampus and dorsal lumbar spinal cord in rats.

Chronic pain has been reported to induce apoptosis. Both chronic excitation of neural pathways involved in pain transmission and control and the stress of pain may be potentially involved in apoptosis induced by pain. Here, we have investigated their possible role in pain-induced apoptosis. Inflammatory pain was induced by injection of formalin in intact and adrenalectomized (ADX) rats. Following exposure to repeated injections of 5% formalin, we detected Bax, Bcl-2, pro-caspase and activated caspase-3 proteins using immunoblotting. The results were compared with those obtained from animals suffered from chronic immobilization stress (IMO). These results showed an increased ratio of Bax/Bcl-2 and activated caspase-3 in hippocampus and dorsal lumbar spinal cord of animals treated with pain and IMO stress; these effects were reduced in ADX animals. On the other hand, the remaining apoptotic effect of pain in adrenalectomized rats was also significant. We surmise that both chronic neural activation and the stress induced by pain are involved in pain-induced apoptosis.

The role of galanin receptors in anticonvulsant effects of low-frequency stimulation in perforant path-kindled rats.

Low-frequency stimulation (LFS) has antiepileptogenic effects on kindled seizures. In the present study, the role of galanin receptors in the inhibitory effect of LFS on perforant path kindling acquisition was investigated in rats. Animals were kindled by perforant path stimulation in a rapid kindling manner (six stimulations per day). LFS (0.1 ms pulses at 1 Hz, 600 pulses, and 80-150 microA) was applied immediately after termination of each kindling stimulation. M35 (0.5 and 1.0 nM per site), a nonselective galanin receptor antagonist and M871 (1.0 microM per site), a selective galanin receptor type 2 (GalR2) antagonist, were daily microinjected into the dentate gyrus before starting the stimulation protocol. The expression of GalR2 in the dentate gyrus was also investigated using semi-quantitative RT-PCR. Application of LFS significantly retarded the kindling acquisition and delayed the expression of different kindled seizure stages. In addition, LFS significantly reduced the increment of daily afterdischarge duration during kindling development. Intra-dentate gyrus microinjection of both M35 and M871 significantly prevented the inhibitory effects of LFS on kindling parameters. During the focal kindled seizure stages (1-3) M871 had no significant effect. However, during generalized seizure stages (4 and 5), M871 had the same effect as M35. Semi-quantitative RT-PCR also showed that after kindling acquisition, the GalR2 mRNA level decreased in the dentate gyrus but application of LFS prevented this decrease. Obtained results show that activation of galanin receptors by endogenous galanin has a role in mediating the inhibitory effect of LFS on perforant path-kindled seizures. This role is exerted through GalR1 during focal- and through GalR2 during generalized-kindled seizures.

Anti-inflammatory and antipyretic effects of Trigonella foenum-graecum leaves extract in the rat.

Anti-inflammatory and antipyretic effects of the Trigonella foenum-graecum (TFG) leaves extract, an Iranian medicinal plant, were examined. For anti-inflammatory activity, the formalin-induced edema model was used. Hyperthermia was induced by intraperitoneal injection of 20% (w/v) aqueous suspension of brewer's yeast. Sodium salicylate (SS) was used as a positive control. Both TFG and SS significantly reduced formalin-induced edema in single dose (TFG 1000 and 2000 mg/kg, SS 300 mg/kg) and chronic administration (TFG 1000 mg/kg and SS 300 mg/kg). TFG and SS also significantly reduced hyperthermia induced by brewer's yeast in 1 and 2 h after their administration. The results indicate that the TFG leaves extract possess anti-inflammatory as well as antipyretic properties in both i.p. and p.o. administration. Phytochemical studies indicate that alkaloids, cardiac glycosides, and phenols are the major component in the extract. Although existence of three anti-inflammatory, analgesic and antipyretic effects in this extract suggest a NSAID-like mechanism for it, but the presence of alkaloids, the absence of other effective compounds such as flavonoids, saponins, steroids, etc., and also its analgesic effect on tail-flick test that usually is not produced by NSAIDs, suggest another mechanism for the extract. So the possibility of alkaloids as effective compounds, in this extract, increases.

An accurate and simple method for measurement of paw edema.

Several methods for measuring inflammation are available that rely on the parameters changing during inflammation. The most commonly used methods estimate the volume of edema formed. In this study, we present a novel method for measuring the volume of pathologically or artificially induced edema. In this model, a liquid column is placed on a balance. When an object is immersed, the liquid applies a force F to attempt its expulsion. Physically, F is the weight (W) of the volume of liquid displaced by that part of the object inserted into the liquid. A balance is used to measure this force (F=W).Therefore, the partial or entire volume of any object, for example, the inflamed hind paw of a rat, can be calculated thus, using the specific gravity of the immersion liquid, at equilibrium mass/specific gravity=volume (V). The extent of edema at time t (measured as V) will be V(t)-V(o). This method is easy to use, materials are of low cost and readily available. It is important that the rat paw (or any object whose volume is being measured) is kept from contacting the wall of the column containing the fluid whilst the value on the balance is read.

Antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit extract.

In this study, probable antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit components, were evaluated. For evaluation of antinociceptive effects, the chronic (formalin test) and acute (tail-flick) pain models of rats were used. For the anti-inflammatory effects, the paw inflammation model was used through subcutaneous injection of 5% formalin to the paw of male rats. Water extracts of the fruit and its components in the single dose were assessed through comparison with the antinociceptive and anti-inflammatory effects of sodium salicylate (SS) as a positive control. Administration of 300 mg/kg of SS (i.p.) had no effect on tail flick latency, while 1000 mg/kg of total (i.p. and p.o.) and endocarp (i.p.) extract, increased this latency (P<0.01, P<0.001, respectively), which was not reversed by naloxone (2 mg/kg). In the formalin test, SS (300 mg/kg, i.p.) and the extract (1000 mg/kg, p.o. ) alleviated the animals nociception in the second phase, while in the first phase they were not effective. The total and endocarp extracts (1000 mg/kg, i.p.) showed a significant effect on both phases (P<0.01, P<0.001, respectively) which was also not reversed by naloxone (2 mg/kg, i.p.). In the acute anti-inflammatory test, the total extract and the aqueous extract of individual fruit components showed a significant effect (P<0.001). This anti-inflammatory effect was not significant compared with the anti-inflammatory effect of SS. Because of the extract effect on the tail-flick latency and both phases of the formalin test, the site of its analgesic action is probably central, and the mechanism of antinociceptive action of the extract are not related to the opioid system. Our phytochemical studies indicated that aqueous extract of E. angustifolia fruit contains flavonoids, terpenoids and cardiac glycosides.

Antinociceptive effects of Trigonella foenum-graecum leaves extract.

There are some reports concerning the antinociceptive effects of the plant Trigonella foenum-graecum (TFG) in Iranian traditional medicine. Because of the side effects of nonsteroidal anti-inflammatory and antinociceptive drugs, and in search for more potent and less harmful compounds, we tried to study the antinociceptive effects of TFG leaves by using tail-flick and formalin tests. Intraperitoneal (i.p.) administration of 500 mg/kg of TFG extract and 100 and 300 mg/kg of sodium salicylate (SS), as a positive control, did not show any effect in the tail-flick test, but the 1000 and 2000 mg/kg of the extract produced significant increase in the tail-flick latency. SS (300 mg/kg, i.p.) induced antinociception in the second phase of the formalin test. TFG (500 mg/kg, i.p.) demonstrated antinociception only in the first phase, but 1000 and 2000 mg/kg, i.p. doses alleviated the pain in both phases. Preliminary LD50 of the extract was very close to 4000 mg/kg, i.p. We conclude that: (1) the extract of TFG leaves produces antinociceptive effects through central and peripheral mechanisms; (2) the antinociceptive effects of 2000 mg/kg of the extract was more potent than 300 mg/kg of SS.